It is now increasingly apparent that modifier genes have a considerable role to play in phenotypic variations of single-gene disorders. Intrafamilial variations, altered penetrance, and altered severity are now common features of single gene disorders because of the involvement of several genes in the expression of the disease phenotype. Oligogenic disorders occur because of a second gene modifying the action of a dominant gene. It is now certain that cancer occurs due to the action of the environment acting in combination with several genes. Although modifier genes make it impossible to predict phenotype from the genotype and cause considerable difficulties in genetic counseling, they have their uses. In the future, it is hoped that modifier genes will allow us to understand cell and protein interactions and thus allow us to understand the pathogenesis of disease.