Past studies highlight a narrowing gender gap and the existence of a shared etiology across substances of abuse; however, few have tested developmental models using longitudinal data. We present data on developmental trends of alcohol, tobacco, and marijuana use, abuse and dependence assessed during adolescence and young adulthood in a community-based Colorado twin sample of 1733 respondents through self-report questionnaires and structured psychiatric interviews. Additionally, we report on the rates of multiple substance use and disorders at each developmental stage, and the likelihood of a substance use disorder (SUD; i.e., abuse or dependence) diagnosis in young adulthood based on adolescent drug involvement. Most notably, we evaluate whether the pattern of multiple substance use and disorders and likelihood ratios across substances support a model of generalized risk. Lastly, we evaluate whether the ranked magnitudes of substance-specific risk match the addiction liability ranking. Substance use and SUDs are developmental phenomena, which increase from adolescence to young adulthood with few and inconsistent gender differences. Adolescents and young adults are not specialized users, but rather tend to use or abuse multiple substances increasingly with age. Risk analyses indicated that progression toward a SUD for any substance was increased with prior involvement with any of the three substances during adolescence. Despite the high prevalence of alcohol use, tobacco posed the greatest substance-specific risk for developing subsequent problems. Our data also confirm either a generalized risk or correlated risk factors for early onset substance use and subsequent development of SUDs.