Laboratory selection experiments play a prominent role in understanding organismal adaptation. Although bacteria are not yet commonly used for such experiments, they are well suited for analyses of both the organismic and the genetic basis of adaptation. Bacteria can be maintained in large populations while occupying limited laboratory space, have short generation times, are well characterized physiologically, biochemically, and genetically, and are readily frozen and revived from the freezer. In addition, the genomes of many species are completely sequenced and knowledge of gene function is unparalleled. Here we review general aspects of selection experiments, the history of using selection experiments in combination with thermal biology and genomics, and highlight findings from six lines of Escherichia coli adapted to high temperature (41.5°C), including changes in organismal fitness, physiological performance, gene complement and gene expression. Our results are an example of the powerful insights that can be discovered by combining the tools and analyses of many biological disciplines including genomics, evolutionary biology, genetics, and evolutionary physiology.