High throughput sequencing assays have given rise to the field of genomics and transformed biomedical research into a computational science. Due to the large size of genomics datasets, high-performance computing is essential for analysis. Galaxy (http://galaxyproject.org) is a popular Web-based platform that can be used for all facets of genomic analyses, including data retrieval and integration, multi-step analysis, repeated analyses via workflows, visualization, collaboration, and publication. This paper describes Galaxy and discusses four lessons learned from the development of Galaxy. First, Galaxy uses open, extensible frameworks so that it can be adapted to new technologies as they become available. Second, by leveraging Web technologies, Galaxy makes genomics tools accessible to everyone and provides a common platform for collaboration. Third, Galaxy fosters community amongst both developers and users and encourages each community to adapt and extend Galaxy to meet their needs. Finally, Galaxy software development and genomic research are closely coupled, and challenges encountered during genomic research drive Galaxy development.