This review focuses on two genetic disorders of metal metabolism, genetic hemochromatosis and Wilson disease, and on the most common lysosomal storage disorder, Gaucher disease, for which recombinant enzyme replacement therapy is available. The discovery of the genes for these disorders has led to an explosion of new information about the function of these gene products and the identification of other proteins involved in their metabolism. These discoveries have altered our current diagnostic and therapeutic approaches to these disorders and have furthered our understanding of disease pathophysiology. New modalities being developed for future use include cell transplant and genetic replacement therapies.