Nongenetic factors have a major influence on psychopathology. Knowledge on specific psychosocial risk and protective mechanisms is more limited because of inadequate attention to measurement issues, person effects on the environment, and the possibility of genetic mediation. Nevertheless, a range of research strategies may be used to provide rigorous tests of causal hypotheses; these have shown the importance of environmentally mediated risks. Challenges for the future include greater use of such research strategies, improved measures of psychosocial risks that can be applied to large samples, investigation of origins of risks, identification of causes of time trends in levels of psychopathology, delineation of psychosocial effects on lifetime liability, understanding of environmental effects on the organism, appreciation of processes involved in developmental programming, and understanding of individual differences in susceptibility.