The study describes the knowledge of and attitudes toward substance use among street-involved youth in Kenya, and how they relate to their substance use practices. In 2011, 146 children and youth ages 10–19 years, classified as either children on the street or children of the street were recruited to participate in a cross-sectional survey in Eldoret, Kenya. Bivariate analysis using χ2 or Fisher’s Exact Test was used to test the associations between variables, and multiple logistic regression analysis was used to identify independent covariates associated with lifetime and current drug use. The study’s limitations and source of funding are noted.