Our study explores the clinical and non-clinical characteristics associated with medication use among children with serious emotional disturbance who are referred into community-based family-driven system of care settings. Using data collected as part of the Comprehensive Community Mental Health Services for Children and Their Families Program initiative, our study provides results from analyses completed on 7,009 children and adolescents with serious emotional disturbance. Using both bivariate and multivariate statistical analyses, the researchers found that females entering systems of care were less likely to have received medication in the 6-months prior to entry, as were children of African-American and Native-American heritage compared to children from non-Hispanic White heritage. Children referred from mental health, child welfare or who were self-referred were more likely to use medications than those referred from juvenile justice. Children with histories of prior inpatient, outpatient, day treatment, or school-based services were between 2 and 4 times more likely to use medications than children without such histories. Children with family histories of mental illness and those who were Medicaid recipients were also more likely to use medications. Family income was also positively related to medication use and younger children were more likely to use medications than older children. Implications of the findings are discussed.