According to models of differential susceptibility, the same neurobiological and temperamental traits that determine increased sensitivity to stress and adversity also confer enhanced responsivity to the positive aspects of the environment. Differential susceptibility models have expanded to include complex developmental processes in which genetic variation interacts with exposure to early environmental factors, such as prenatal stress hormones and family conflict. In this study I employed a simulation approach to explore whether, and under what conditions, developmental models of differential susceptibility are compatible with the cumulative findings from twin studies of personality and behavior, which consistently show sizable effects of genetic and nonshared environmental factors and small to negligible effects of the shared environment. Simulation results showed that, to a first approximation, current alternative models of differential susceptibility are all equally compatible with the evidence from twin research; that sizable interaction effects involving individual differences in plasticity are plausible, but only if direct environmental effects are correspondingly weak; and that a major role of shared environmental factors is plausible in early development (consistent with the developmental mechanisms postulated in the differential susceptibility literature) but not in later development. These results support the general plausibility of differential susceptibility models and suggest some realistic constraints on their assumptions.