A life stage perspective is necessary for development of age-appropriate strategies to address substance use disorders (SUDs) and related health conditions in order to produce better overall health and well-being. The current review evaluated the literature across three major life stages: adolescence, adulthood, and older adulthood. Findings: 1) Substance use is often initiated in adolescence, but it is during adulthood that prevalence rates for SUDs peak; and while substance involvement is less common among older adults, the risk for health complications associated with use increases. 2) Alcohol, tobacco, marijuana, and, increasingly, prescription medications, are the most commonly misused substances across age groups; however, the use pattern of these and other drugs and the salient impact vary depending on life stage. 3) In terms of health outcomes, all ages are at risk for overdose, accidental injury, and attempted suicide. Adolescents are more likely to be in vehicular accidents while older adults are at greater risk for damaging falls. Adulthood has the highest rates of associated medical conditions (e.g., cancer, sexually transmitted disease, heart disease) and mental health conditions (e.g., bipolar disorder, anxiety disorders, antisocial personality disorder). Conclusion: Prolonged heavy use of drugs and/or alcohol results in an array of serious health conditions. Addressing SUDs from a life stage perspective with assessment and treatment approaches incorporating co-occurring disorders are necessary to successfully impact overall health.