Understanding the biology of mental illness would be a paradigm shift in our thinking about mind. It would not only inform us about some of the most devastating diseases of humankind but, because these are diseases of thought and feeling, it would also tell us more about who we are and how we function. I naively thought we were on the verge of such a paradigm change in 1983, when James Gusella and Nancy Wexler were tracking down the gene that causes Huntington's disease. I expected that within 10 years we would have found the major genes that contribute to schizophrenia, depression, and autism. Since then, there has been a lot of enthusiasm about genes and mental illness and some false starts, but surprisingly little progress.