This longitudinal study examines individual differences in the tendency to initiate (N = 4,612) and escalate (N = 2,837) smoking when adolescents gain a best friend who smokes. Potential moderating factors include self-esteem, depression, problem behavior, school and family bonds, and household access to cigarettes. In addition to acquiring a smoking best friend, initiation was predicted by trouble at school, household access, poorer grades and delinquency, whereas escalation was predicted by depressive symptoms. There was little evidence that the examined individual difference factors moderate the association between gaining a smoking best friend and increased adolescent smoking. Results point to the challenges of identifying factors that may lead adolescents to be more or less susceptible to the influence of pro-smoking friends.