This study examined whether interactions of parental knowledge of adolescent’s whereabouts with impulsivity and sensation seeking in the prediction of adolescent substance use supported the diathesis–stress or differential susceptibility model in 230 15-year old adolescents (53% girls). Interactions between impulsivity and parental knowledge supported the diathesis–stress model with high impulsivity as a vulnerability factor: when impulsivity was higher, low levels of parental knowledge were associated with higher levels of substance use. Interactions between sensation seeking and parental knowledge supported differential susceptibility with low sensation seeking as a susceptibility factor; low parental knowledge was associated with higher substance use and high parental knowledge with lower substance use when sensation seeking was lower. Our results show that impulsivity and sensation seeking should be considered independently. Results support previous research suggesting that impulsivity in adolescence may act as a vulnerability factor and suggests that low sensation seeking may be a susceptibility factor.