Multisystemic therapy (MST) is effective for decreasing or preventing delinquency and other externalizing behaviors and increasing prosocial or adaptive behaviors. The purpose of this project was to review the literature examining the efficacy of MST for other child psychological and health problems reflecting non-externalizing behaviors, specifically difficulties related to child maltreatment, serious psychiatric illness [Serious psychiatric illness was defined throughout the current review paper as the “presence of symptoms of suicidal ideation, homicidal ideation, psychosis, or threat of harm to self or others due to mental illness severe enough to warrant psychiatric hospitalization based on the American Academy of Child and Adolescent Psychiatry (Level of care placement criteria for psychiatric illness. American Academy of Child and Adolescent Psychiatry, Washington, DC, 1996) level of care placement criteria for psychiatric illness” (Henggeler et al. in J Am Acad Child Psy 38:1331–1345, p. 1332, 1999b). Additionally, youth with “serious emotional disturbance (SED)” defined as internalizing and/or externalizing problems severe enough to qualify for mental health services in public school who were “currently in or at imminent risk of a costly out-of-home placement” (Rowland et al. in J Emot Behav Disord 13:13–23, pp. 13–14, 2005) were also included in the serious psychiatric illness category.], and health problems (i.e., obesity and treatment adherence for diabetes). PubMed, Web of Science, MEDLINE, and PsycINFO databases; Clinicaltrials.gov; DARE; Web of Knowledge; and Cochrane Central Register of Controlled Trials were searched; and MST developers were queried to ensure identification of all relevant articles. Of 242 studies identified, 18 met inclusion criteria for review. These were combined in a narrative synthesis and critiqued in the context of review questions. Study quality ratings were all above mean scores reported in prior reviews. Mixed support was found for the efficacy of MST versus other treatments. In many cases, treatment effects for MST or comparison groups were not sustained over time. MST was efficacious for youth with diverse backgrounds. No studies discussed efficacy of MST provided in different treatment settings. Four studies found MST more cost-effective than a comparison treatment, leading to fewer out-of-home placements for youth with serious psychiatric illness or lower treatment costs for youth with poorly controlled diabetes.