Prescription drug misuse is a growing public health concern and has been understudied in Latino populations. The current study tests the relationships between childhood and family characteristics and prescriptions drug misuse among adult Latinos. A subsample of 8,308 Latinos from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Logistic regression analyses tested associations between parental alcoholism, parental divorce before age 18, and parental death before age 18 and prescription drug misuse and prescription drug use disorder. Parental alcoholism and parental divorce increased the odds of both prescription drug misuse and use disorder. Parental death increased the odds of prescription drug use disorders. The results have important implications for understanding the complex associations between family psychosocial history and prescription drug misuse.