The elucidation of the human and mouse genomes provides new opportunities for exploring the genetic underpinnings of complex mammalian behaviors. This information also provides new windows into the pathophysiology and treatment of neuropsychiatric diseases. Optimal use of the rapidly escalating numbers of mouse lines engineered for these purposes is hindered, however, by practical and theoretical limitations of common behavioral analyses. New strategies combining automated behavioral monitoring and information technologies are currently under development in both academic and industrial settings. These hold promise, both for improving the throughput of mouse behavioral assessment and for providing new insights into the neurobiology of mammalian behavioral regulation.