This book chapter provides information on two substance use and mental health interventions for homeless youth--the community reinforcement approach (CRA) and motivational enhancement therapy (MET). An estimated 48 percent to 98 percent of youth who are homeless meet criteria for at least one mental health diagnosis, including depressive disorders, anxiety disorders, posttraumatic stress disorder, psychosis, and attention-deficit/hyperactivity disorder. Between 69 percent and 86 percent meet criteria for a substance use disorder. Youth who are homeless have elevated rates of co-occurring substance use and mental health disorders when compared with their housed peers. Left untreated, substance use and mental health problems create additional barriers to exiting homelessness. Intervention efforts to improve the lives of these youth may have limited impact if underlying substance use and mental health problems are not treated. Research has shown that using CRA and MET has been effective among homeless youth. Youth who participated in CRA reported increases in social stability and decreases in drug use and depression compared with usual treatment. MET has been associated with similar positive outcomes. The book chapter describes the theoretical basis for both interventions, as well as program components and implementation considerations.