Researchers and clinicians are increasingly recognizing that psychological and psychiatric disorders are often developmentally progressive, and that diagnosis often represents a point along that progression that is defined largely by our abilities to detect symptoms. As a result, strategies that guide our searches for the root causes and etiologies of these disorders are beginning to change. This review describes interactions between genetics and experience that influence the development of psychopathologies. Following a discussion of normal brain development that highlights how specific cellular processes may be targeted by genetic or environmental factors, we focus on four disorders whose origins range from genetic (fragile X syndrome) to environmental (fetal alcohol syndrome) or a mixture of both factors (depression and schizophrenia). C.H. Waddington's canalization model (slightly modified) is used as a tool to conceptualize the interactive influences of genetics and experience in the development of these psychopathologies. Although this model was originally proposed to describe the ‘canalizing’ role of genetics in promoting normative development, it serves here to help visualize, for example, the effects of adverse (stressful) experience in the kindling model of depression, and the multiple etiologies that may underlie the development of schizophrenia. Waddington's model is also useful in understanding the canalizing influence of experience-based therapeutic approaches, which also likely bring about ‘organic’ changes in the brain. Finally, in light of increased evidence for the role of experience in the development and treatment of psychopathologies, we suggest that future strategies for identifying the underlying causes of these disorders be based less on the mechanisms of action of effective pharmacological treatments, and more on increased knowledge of the brain's cellular mechanisms of plastic change.