VCell (Virtual Cell) is a comprehensive platform for modeling cell biological systems that is built on a central database and disseminated as a web application. VCell permits construction of models, application of numerical solvers to perform simulations, and analysis of simulation results, offering the choice of multiple physical approximations and simulation technologies to appropriately model a particular system. The BioModel interface provides an intuitive interface to construct models using either pathway diagrams or rules and from a single model of the physiology allows a choice of compartmental (0 dimensions) or spatial (1,2 or3 dimensions) applications of the physiology that can apply stochastic, determistic, or hybrid stochastic/deterministic solvers. Applications are automatically translated into full mathematical descriptions of reaction and diffusion systems and then solved via fully validated numerical methods. A MathModel interface provides a direct interface to develop models using a math description language. VCell supports multiple biophysical mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion and electrophysiology. VCell is developed by the National Resource for Cell Analysis and Modeling, supported by NIGMS.