At the time of entry into residential treatment, many youth have prescriptions for one or more psychotropic medications. It is not well understood why some youth are prescribed only one psychotropic medication while others may be prescribed more. We sought to determine if differences existed between youth entering residential treatment with monopharmacy (n = 77) versus youth entering with polypharmacy (n = 103). Youth were compared across demographic, family, behavioral, mental health, and psychotropic medication variables. The only significant differences identified were related to the numbers of youth with prescriptions across the different psychotropic classes. As would be expected, youth experiencing polypharmacy were more likely to have prescriptions within each class. Implications, limitations, and recommendations for future research are discussed. (Contains 3 tables.)