Thanks to their short generation times and large population sizes, microbes evolve rapidly. Evolutionary biologists have exploited this to observe evolution in real time. The falling costs of whole-genome sequencing using next-generation technologies now mean that it is realistic to use this as a tool to study this rapid microbial evolution both in the laboratory and in the wild. Such experiments are being used to accurately estimate the rates of mutation, reveal the genetic targets and dynamics of natural selection, uncover the correlation (or lack thereof) between genetic and phenotypic change, and provide data to test long-standing evolutionary hypotheses. These advances have important implications for our understanding of the within- and between-host evolution of microbial pathogens.