The developmental interplay between nature and nurture is discussed, with particular reference to implications for research in developmental psychopathology. The general principles include individual differences in reactivity to the environment, two-way interplay between intraindividual biology and environmental influences, and the need to consider broader social contextual features. Individuals actively process their experiences; they also act on their environment to shape and select their experiences, and individual characteristics change over time. Key findings on genetic effects include their ubiquitous influence, the multifactorial origin of most psychopathology, the involvement of several genes in most mental disorders, some genetic effects operate through dimensional risk features rather than directly on disorder, some genetic effects are dependent on gene–environment correlations and interactions, and genetic effects increase with age. Key findings on environmental effects include their ubiquitous influence, the genetic mediation of some supposed environmental effects, the importance of passive gene–environment correlations, the paucity of evidence regarding environmental effects on lifetime liability to psychopathology, the lack of understanding of environmental effects on the organism, and the importance of nonshared environmental effects. Research strategies to investigate environmental risk mediation include the range of genetically sensitive designs, migration studies, secular trend investigations, studies of nonfamilial environments, and examination of intraindividual change in relation to measured environmental alterations. Proximal processes involved in person–environment interplay are discussed in relation to person–environment interactions and evocative and active person–environment correlations.