Type 2 diabetes now affects more than 1 in 10 US adults and is a leading cause of morbidity, mortality, and healthcare expense. There are increasing numbers of available pharmacotherapies, with established agents as well as newer drugs developed from hormones in the incretin pathway, among others. New data are accumulating continuously with respect to potential benefits of both long-standing and new agents, as well as risks identified through post-marketing surveillance. Here we review the commonly prescribed pharmacotherapy options with attention to recently published information and provide a rational approach to choice of therapy.