Technological advances are making large-scale measurements of microbial communities commonplace. These newly acquired datasets are allowing researchers to ask and answer questions about the composition of microbial communities, the roles of members in these communities, and how genes and molecular pathways are regulated in individual community members and communities as a whole to effectively respond to diverse and changing environments. In addition to providing a more comprehensive survey of the microbial world, this new information allows for the development of computational approaches to model the processes underlying microbial systems. We anticipate that the field of computational microbiology will continue to grow rapidly in the coming years. In this manuscript we highlight both areas of particular interest in microbiology as well as computational approaches that begin to address these challenges.