Our ability to connect positive selection with function remains rudimentary, but gradual progress is being made. As additional sequence data becomes available, it will become possible to associate selection with individual residues of proteins with greater accuracy. At the same time, more data is becoming available on the specific functional roles of individual amino acids, for example, from structural or mutagenesis studies. As a result, it will increasingly become possible to find direct links between selection and function. Often these links will initially be tentative, as in our site-specific analysis of the HAVCR1 gene. Nevertheless, they provide a valuable starting point for experimental follow-up. At the same time, more can be done to incorporate non-sequence data-such as structural and expression data-into computational methods for detecting positive selection. Thus, improvements in both computational and experimental methods will be needed to establish deeper and more informative connections between evolutionary dynamics and molecular function.