The discovery of genes encoding maturity onset diabetes of the young (MODY) type 2 diabetes mellitus (T2DM) represents a milestone in the study of the genetics of complex diseases. The genes were revealed, in large part, through positional cloning and linkage analysis in families. The genes are relatively rare and have strong genotype-phenotype correlations. Based on the results of several genome scans for genes encoding T2DM in various racial-ethnic groups, it appears that, as in other complex diseases, multiple genes are involved, each contributing a small amount to the overall risk. New strategies for patient sampling, phenotyping, genotyping technologies and genetic analysis must be employed to further define the genetic basis of this disease.