# Unlocking Guidance for Discrete State-Space Diffusion and Flow Models

arXiv: https://arxiv.org/abs/2406.01572 · HTML: https://mlsanity.com/paper/2406.01572/

## Key facts

- Cited by 129 papers in the map (data through 14 Oct 2026).
- Builds on 56 of its 101 references that are in the map.
- First posted on arXiv 3 Jun 2024.

## Builds on (most cited first, 30 of 56)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Proximal Policy Optimization Algorithms](https://mlsanity.com/paper/1707.06347/) (2017)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Direct Preference Optimization: Your Language Model is Secretly a Reward Model](https://mlsanity.com/paper/2305.18290/) (2023)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Improved Techniques for Training GANs](https://mlsanity.com/paper/1606.03498/) (2016)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Diffusion-LM Improves Controllable Text Generation](https://mlsanity.com/paper/2205.14217/) (2022)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Plug and Play Language Models: A Simple Approach to Controlled Text Generation](https://mlsanity.com/paper/1912.02164/) (2019)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [SiT: Exploring Flow and Diffusion-based Generative Models with Scalable Interpolant Transformers](https://mlsanity.com/paper/2401.08740/) (2024)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Argmax Flows and Multinomial Diffusion: Learning Categorical Distributions](https://mlsanity.com/paper/2102.05379/) (2021)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [A Continuous Time Framework for Discrete Denoising Models](https://mlsanity.com/paper/2205.14987/) (2022)
- [DiffuSeq: Sequence to Sequence Text Generation with Diffusion Models](https://mlsanity.com/paper/2210.08933/) (2022)
- [FUDGE: Controlled Text Generation With Future Discriminators](https://mlsanity.com/paper/2104.05218/) (2021)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (2022)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [Reduce, Reuse, Recycle: Compositional Generation with Energy-Based Diffusion Models and MCMC](https://mlsanity.com/paper/2302.11552/) (2023)
- [Continuous diffusion for categorical data](https://mlsanity.com/paper/2211.15089/) (2022)

## Built on by (most cited first, 30 of 129)

- [Simplified and Generalized Masked Diffusion for Discrete Data](https://mlsanity.com/paper/2406.04329/) (2024)
- [Block Diffusion: Interpolating Between Autoregressive and Diffusion Language Models](https://mlsanity.com/paper/2503.09573/) (2025)
- [Remasking Discrete Diffusion Models with Inference-Time Scaling](https://mlsanity.com/paper/2503.00307/) (2025)
- [Simple Guidance Mechanisms for Discrete Diffusion Models](https://mlsanity.com/paper/2412.10193/) (2024)
- [Derivative-Free Guidance in Continuous and Discrete Diffusion Models with Soft Value-Based Decoding](https://mlsanity.com/paper/2408.08252/) (2024)
- [The Diffusion Duality](https://mlsanity.com/paper/2506.10892/) (2025)
- [Inference-Time Alignment in Diffusion Models with Reward-Guided Generation: Tutorial and Review](https://mlsanity.com/paper/2501.09685/) (2025)
- [Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design](https://mlsanity.com/paper/2410.13643/) (2024)
- [Discrete Diffusion in Large Language and Multimodal Models: A Survey](https://mlsanity.com/paper/2506.13759/) (2025)
- [Flow Matching with General Discrete Paths: A Kinetic-Optimal Perspective](https://mlsanity.com/paper/2412.03487/) (2024)
- [Edit Flows: Flow Matching with Edit Operations](https://mlsanity.com/paper/2506.09018/) (2025)
- [GenMol: A Drug Discovery Generalist with Discrete Diffusion](https://mlsanity.com/paper/2501.06158/) (2025)
- [How Discrete and Continuous Diffusion Meet: Comprehensive Analysis of Discrete Diffusion Models via a Stochastic Integral Framework](https://mlsanity.com/paper/2410.03601/) (2024)
- [Fast Solvers for Discrete Diffusion Models: Theory and Applications of High-Order Algorithms](https://mlsanity.com/paper/2502.00234/) (2025)
- [Fine-Tuning Discrete Diffusion Models with Policy Gradient Methods](https://mlsanity.com/paper/2502.01384/) (2025)
- [PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion](https://mlsanity.com/paper/2412.17780/) (2024)
- [Dynamic Search for Inference-Time Alignment in Diffusion Models](https://mlsanity.com/paper/2503.02039/) (2025)
- [Esoteric Language Models: A Family of Any-Order Diffusion LLMs](https://mlsanity.com/paper/2506.01928/) (2025)
- [Continuously Augmented Discrete Diffusion model for Categorical Generative Modeling](https://mlsanity.com/paper/2510.01329/) (2025)
- [Steering Masked Discrete Diffusion Models via Discrete Denoising Posterior Prediction](https://mlsanity.com/paper/2410.08134/) (2024)
- [Debiasing Guidance for Discrete Diffusion with Sequential Monte Carlo](https://mlsanity.com/paper/2502.06079/) (2025)
- [d2: Improving Reasoning in Diffusion Language Models via Trajectory Likelihood Estimation](https://mlsanity.com/paper/2509.21474/) (2025)
- [Reward-Guided Iterative Refinement in Diffusion Models at Test-Time with Applications to Protein and DNA Design](https://mlsanity.com/paper/2502.14944/) (2025)
- [Target Concrete Score Matching: A Holistic Framework for Discrete Diffusion](https://mlsanity.com/paper/2504.16431/) (2025)
- [Training-Free Guidance Beyond Differentiability: Scalable Path Steering with Tree Search in Diffusion and Flow Models](https://mlsanity.com/paper/2502.11420/) (2025)
- [Language Modeling with Hyperspherical Flows](https://mlsanity.com/paper/2605.11125/) (2026)
- [Diffuse Everything: Multimodal Diffusion Models on Arbitrary State Spaces](https://mlsanity.com/paper/2506.07903/) (2025)
- [MDNS: Masked Diffusion Neural Sampler via Stochastic Optimal Control](https://mlsanity.com/paper/2508.10684/) (2025)
- [Beyond Masked and Unmasked: Discrete Diffusion Models via Partial Masking](https://mlsanity.com/paper/2505.18495/) (2025)
- [Discrete Diffusion Models: Novel Analysis and New Sampler Guarantees](https://mlsanity.com/paper/2509.16756/) (2025)

## Abstract (arXiv)

Generative models on discrete state-spaces have a wide range of potential applications, particularly in the domain of natural sciences. In continuous state-spaces, controllable and flexible generation of samples with desired properties has been realized using guidance on diffusion and flow models. However, these guidance approaches are not readily amenable to discrete state-space models. Consequently, we introduce a general and principled method for applying guidance on such models. Our method depends on leveraging continuous-time Markov processes on discrete state-spaces, which unlocks computational tractability for sampling from a desired guided distribution. We demonstrate the utility of our approach, Discrete Guidance, on a range of applications including guided generation of small-molecules, DNA sequences and protein sequences.