The Minnesota Twin Family Study is a longitudinal study of 11-year-old and 17-year-old twins and their parents designed to examine factors related to the etiology of substance abuse and related problems. At study intake, the twins and their parents participate in a day-long assessment in our laboratory that includes measures of endophenotypes (e.g., event-related potentials, EEG, autonomic nervous system reactivity, startle eye-blink), psychopathology, personality, cognitive ability, anthropometry, and environmental risk/protective factors. DNA derived from blood is also collected. A parallel longitudinal study of adolescent adoptive siblings, biologically related siblings, and their parents is also underway. Over 1500 twin families and 350 adoptive and biological sibling families have already entered the longitudinal phase of the study. This article provides an overview of study methods, highlights published findings, and describes procedures in place to foster collaboration with other investigators.