We have made remarkable progress in understanding the molecular bases of many Mendelian diseases over the past 2-3 decades. The current interest in discovering the molecular basis of complex diseases uses either linkage or candidate gene approaches. The latter often uses case/control (or case/cohort) study designs. We believe it is critically important to have a thorough understanding of SNP (single nucleotide) and haplotype function in such endeavors. Functionally neutral SNPs and haplotypes are probably best suited for linkage studies (far away from the locus of interest). Functionally relevant SNPs and haplotypes seem best suited for candidate gene approaches. The need for functional data may result in a renaissance of biochemical genetics with a new twist in the genomic era. We propose that the functional characterization of SNPs and haplotypes be advanced with great vigor for those genes with defined assayable phenotypes. These systematic investigations will involve classical biochemistry, modern genetics, and genomics and will probably also draw on newer technologies such as microarrays. In short, a renaissance of biochemical genetics will advance our understanding of complex diseases.