Abstract Alcohol, substance and drug use among urban slum adolescents is not only a risky behavior in the era of HIV/AIDS but also a potential security threat to a growing city. Based on the Nairobi Urban Slum Survey, adolescent males are more than 20 times more likely to engage in drugs, and 5 times more likely to consume alcohol than girls. In addition, being out-of-school increases the risk of alcohol and drug abuse. There is a gender dimension to this; societal expectation, division of labor, and nature of upbringing is different for males and females. While the government policy of free primary education is likely to reduce the alcohol and drug incidence, gender targeted interventions, providing alternatives for both boys and girls, would be equally essential.