DARPP-32 is a master molecular regulator in neurons that receive the neurotransmitter dopamine. For over two decades, an intense research effort has demonstrated that DARPP-32 occupies a unique position as a central molecular control point, integrating multiple information streams that converge through a variety of neurotransmitters, neuromodulators, neuropeptides, and steroid hormones onto dopaminoceptive neurons. Since dopaminergic neurotransmission is critical for motivated behavior, working memory, and reward-related learning and is implicated in, among other conditions, schizophrenia, alcoholism, Parkinson's disease, and pathological gambling, DARPP-32 has received considerable attention not only in basic neuroscience, but also in studies of the pathogenesis of these disorders and as a promising target for innovative drug treatment in psychiatry. In addition, DARPP-32 is found in nonneuronal tissues and may have relevance for certain types of cancer.