The past 50 years have seen dramatic changes in childhood psychopathology research. The goal of this overview is to contrast observational and experimental research approaches; both have grown more complex such that the boundary between these approaches may be blurred. Both are essential. Landmark observational studies with long-term follow-up (Robins, 1966; Yarrow, Campbell, & Burton, 1970) have had--and continue to have--unique impact on clinical research and practice. Epidemiological studies showed high rates of psychological disorder and their close tie to neurological impairment (Rutter, Tizard, & Whitemore, 1970). These studies have current impact with respect to brain imaging correlates of clinical outcome. Pharmacological studies, particularly those on stimulants and on treatment of pediatric obsessive compulsive disorder (OCD), have propelled experimental methodology and inspired translational approaches. Predicted future trends are: more informed subgrouping of our heterogeneous phenotypes, reliance on multicenter trials, and documentation of non-conventional methods of care delivery.