The Minnesota Center for Twin and Family Research (MCTFR) houses a collection of longitudinal, community-based twin-family and adoptee-family projects that focus on the mental health outcomes of adolescent youth with a special focus on the development of substance use and related behavior disorders. The Minnesota Twin Family Study includes epidemiological investigations of 11- and 17-year-old twins, an examination of 11-year-old twins selected for being at high risk for having a childhood disruptive behavior disorder, and a supplemental registry of young adult twins age 18 years and older who are not enrolled in these longitudinal studies. Also, part of the MCTFR is the Sibling Interaction and Behavior Study, a complementary prospective investigation of adolescent sibling pairs in families with adoptive and biological offspring. MCTFR participants from these various projects are assessed in person and through multiple informants to provide comprehensive coverage of psychological adjustment, mental health, and psychosocial risk/protective factors. Measurement of EEG and autonomic nervous system reactivity is also part of the assessment battery for twin families. This article provides an overview of study design and includes a review of recent MCTFR findings.