The availability of complete genome sequences and the wealth of large-scale biological datasets provide an unprecedented opportunity to elucidate the genetic basis of human diseases. Here we use integrative in silico approaches to provide an accurate description of gene functions to a set of 1737 highly curated disease genes in the human genome. This analysis is the first attempt on in silico identification of druggable domains within disease genes. We provide information on gene architecture and function, druggability in the context of available drugs, and evolutionary conservation across 38 model eukaryotic genomes. These data could serve as a useful compendium for integrated information on disease genes with the potential for exploring pharmaceutically exploitable targets. Our analyses underscore the utility of large genomic databases for in silico systematic drug target identification in the post-genomic era.