Schizophrenia (SCZ) and bipolar affective disorder (BPAD) (formerly termed manic-depressive illness) are severe, disabling psychiatric illnesses that feature promi- nently in the top ten causes of disability worldwide (Lopez and Murray 1998). Each will affect about 1% of the pop- ulation in their lifetime. The cost of providing treatment for mental illness in the UK National Health Service is es- timated at 10% of total expenditure. The total costs (med- ical, social, economic) are estimated at £32 billion per an- num for the population of 50 million in England (Bird 1999; see also www.mentalhealth.org.uk). World Health Organization predictions indicate that major depression will be second only to heart disease in terms of disability- adjusted life years (DALYs) by 2020 (Lopez and Murray 1998). Research into the causes of these devastating dis- orders and the development of improved interventions is a high scientific, social, individual, and public health prior- ity. Unfortunately, these remain Cinderella disorders com- pared to cancer and heart disease, both in terms of gov- ernmental and societal recognition and national and international research support. Despite their high preva- lence and, indeed, decades of neuroscience research, little is known with certainty about their cellular and molecular bases. Consequently, treatments remain largely empirical and palliative. This apparent impasse, however, justifies neither complacency nor despondency, because the one consistent, replicable finding is that family, twin, and adoption studies demonstrate a major genetic component in both SCZ and BPAD (Merikangas and Risch 2003). A decade ago only a handful of genes for monogenic disor- ders had been positionally cloned through linkage studies. Over the past five years, as the Human Genome Project and associated tools have developed, that number has soared to over 1000. As the Human Genome Project passes from formal completion to full development as a universal biological tool, we can expect accelerated progress in tackling the much more difficult task of genet- ically dissecting the common complex disorders including major mental illness.