BETSE (BioElectric Tissue Simulation Engine) is an open-source cross-platform finite volume simulator for 2D computational multiphysics problems in the life sciences - including electrodiffusion, electro-osmosis, galvanotaxis, voltage-gated ion channels, gene regulatory networks, and biochemical reaction networks (e.g., metabolism). BETSE is portably implemented in pure Python 3, continuously stress-tested with GitHub Actions + pytest + tox, and permissively distributed under the BSD 2-clause license.