Childhood neglect has been cited as a risk factor for later substance abuse and criminal behavior. However, a large body of literature shows that a substantial percentage of neglected and abused individuals do not go on to abuse substances or engage in criminal behavior. The current study investigates whether a genetic variant (serotonin transporter linked polymorphic region [5-HTTLPR]) in the 5-hydroxytryptamine (5-HTT) gene moderates the effect of childhood neglect on alcohol use problems, marijuana use, and criminal behavior. Data from the National Longitudinal Study of Adolescent Health shows that 5-HTTLPR conditions the effect of neglect on marijuana use for females, but not for males. Findings also reveal a significant gene-environment correlation between 5-HTTLPR and neglect for females only. These results suggest that 5-HTTLPR is associated with an increased risk of neglect for females, and it also increases neglected females' risk of abusing marijuana.