Drug-target discovery is fundamentally a ‘wet-bench’ experimental process. Most potential drug targets are identified on a laboratory bench top using genetic screens, biochemical tests or cellular assays. These assays may be done in simple cell cultures, but more often are done using a variety of model organisms. In silico drug-target discovery is possible primarily because of the Human Genome Project and related large-scale sequencing efforts. In contrast to endogenous diseases, the identification of drug targets and the development of drugs to treat exogenous diseases is inherently easier and much more compatible with in silico approaches. When identifying or homing in on endogenous disease targets, one is most often interested in human gene or protein sequences. However, with recent developments in comparative genomics and comparative proteomics using model organisms, there is a growing realization that sequence information from other organisms can also be put to very good use.