One of many publications emanating from the New York Longitudinal Study (NYLS), the prospective study of Stella Chess, Alexander Thomas, and Mahin Hassibi of six cases of depression during childhood and adolescence, which appeared in the Journal of Nervous and Mental Disease in 1983, provides an opportunity to reflect on the climate in which the NYLS was conceived and conducted. Its methodology is reviewed, and principle findings are summarized. In the more than 50 years since the inception of the NYLS, the attention of temperament investigators has shifted from a focus on definition and measurement to the examination of relations between temperament and psychopathology, including the exploration of the neurocircuitry underlying different dimensions of temperament and their contributions to the etiology, pathogenesis, and treatment of axis I disorders in developing children.