We outline an epigenetic approach to understanding the relation between sim
ple dispositional characteristics and complex problem behaviors, with a foc
us on adolescent substance use. Epigenetic theory predicts that effects of
temperament are mediated through self-control and risk-taking tendency, iso
morphic attributes that are based in temperament but represent developmenta
l elaborations of these characteristics. We describe how the research progr
am has confirmed predictions from epigenetic theory, addressed additional q
uestions embodied in the theory, and clarified the multiple pathways from t
emperament characteristics to life stress, social relationships, and motive
s for substance use. In a final section, we discuss implications for the st
udy of problem behavior and psychopathology.