We introduce Pyvolve, a flexible Python module for simulating genetic data along a phylog- eny using continuous-time Markov models of sequence evolution. Easily incorporated into Python bioinformatics pipelines, Pyvolve can simulate sequences according to most stan- dard models of nucleotide, amino-acid, and codon sequence evolution. All model parame- ters are fully customizable. Users can additionally specify custom evolutionary models, with custom rate matrices and/or states to evolve. This flexibility makes Pyvolve a convenient framework not only for simulating sequences under a wide variety of conditions, but also for developing and testing new evolutionary models. Pyvolve is an open-source project under a FreeBSD license, and it is available for download, along with a detailed user-manual and example scripts, from http://github.com/sjspielman/pyvolve.