Researchers in quantitative systems biology make use of a large number of different software packages for modeling, analysis, visualization, and general data manipulation. The Systems Biology Workbench (SBW), is a software framework that allows heterogeneous application components-written in diverse programming languages and running on different platforms-to communicate and use each others' capabilities via a fast binary encoded-message system. Our goal was to create a simple, high performance, open-source software infrastructure which is easy to implement and understand. SBW enables applications (potentially running on separate, distributed computers) to communicate via a simple network protocol. The interfaces to the system are encapsulated in client-side libraries that we provide for different programming languages.