The identification of genes involved in human genetic disease is no longer the province of those who would make a career of 'not finding' a gene. Developments from the human genome initiative have vastly facilitated the process of localizing genetic intervals segregating mutations, as well as that of obtaining the physical regents necessary for characterizing the region. In a few years' time, efforts aimed at the assignment of genes to the physical map, coupled with increasing quantities of sequence data from both cDNA and genomic sources, will provide numerous candidate genes for analysis, with consequences for the approaches used to define the gene and mutations(s) involved in the disease of interest.