Better mechanistic understanding of disease through mapping of the human and mouse genomes enables rethinking of human infirmity. In the case of cancer, e.g., we may begin to associate disease states with their underlying genetic defects rather than with the organ system involved. That will enable more selective, nontoxic therapies in patients who are genetically predisposed to respond to them. Because one of the major goals of molecular imaging research is to interrogate gene expression noninvasively, it can impact greatly on that process. Most of molecular imaging research is undertaken in small animals, which provide a conduit between in vitro studies and human clinical imaging. We are fortunate to be able to manipulate small animals genetically, and to have increasingly better models of human disease. The ability to study those animals noninvasively and quantitatively with new, high-resolution imaging devices provides the most relevant milieu in which to find and examine new therapies.