AbstractComputational modeling has become an established technique to encode mathematical representations of cellular processes and gain mechanistic insights that drive testable predictions. These models are often constructed using graphical user interfaces or domain-specific languages, with SBML used for interchange. Models are typically simulated, calibrated, and analyzed either within a single application, or using import and export from various tools. Here, we describe a programmatic modeling paradigm, in which modeling is augmented with best practices from software engineering. We focus on Python - a popular, user-friendly programming language with a large scientific package ecosystem. Models themselves can be encoded as programs, adding benefits such as modularity, testing, and automated documentation generators while still being exportable to SBML. Automated version control and testing ensures models and their modules have expected properties and behavior. Programmatic modeling is a key technology to enable collaborative model development and enhance dissemination, transparency, and reproducibility.HighlightsProgrammatic modeling combines computational modeling with software engineering best practices.An executable model enables users to leverage all available resources from the language.Community benefits include improved collaboration, reusability, and reproducibility.Python has multiple modeling frameworks with a broad, active scientific ecosystem.