Genes are nonrandomly distributed in the human genome, both within and between chromosomes. Thus, genes of similar function and common evolutionary origin are often clustered, as are genes with similar expression profiles. We now report that the >2400 genes known to underlie human monogenic inherited disease are non-randomly distributed in the genome over and above the general nonrandomness evident in the distribution of human genes. Further, a subset of 315 inherited disease genes subject to gross deletion was found to exhibit a degree of clustering that was twice that manifested by disease genes in general. The clustering of human disease genes is likely to have important implications for understanding the genotype-phenotype relationship in contiguous gene syndromes as well as those conditions characterized by multigene deletions or complex chromosomal rearrangements.