Alert readers will note that, compared with previous annual issues, there is greater coverage of actual disease in this edition of Current Opinion in Genetics & Development. There are two reasons for this. First, a primary motivation for our interest in molecular genetics, as practising clinicians, is that it can improve specifically our understanding of, and therapy for, many diseases. Second, recent progress with the Human Genome Project has put many more diseases within the reach of the genetic approach; this issue illustrates the rich harvest that is resulting.