Objective: To comment on the article in this issue of the Journal by Professor Michael Rutter, "Environmentally Mediated Risks for Psychopathology: Research Strategies and Findings," in the context of current research findings on gene-environment interaction, epigenetics, and gene expression. Method: Animal and human studies are reviewed that differentiate the role of gene expression in developmental biology and psychopathology as well as studies that begin to specify the biological mechanisms involved in determining how genotype is translated into phenotype. Results: Genetic instructions are not translated directly into phenotypic traits but are modified potentially at two levels: the transcription process wherein messenger RNA is produced, and translation when protein synthesis occurs. Interplay of genetic and environmental factors determines the final product of gene expression as measured by the when, where, and amount of protein synthesized. Epigenetic processes may operate at the level of messenger RNA to control gene expression. Conclusions: The field of developmental psychopathology is providing the theoretical and research framework to explore the conceptual space between the genome and the environment. Natural selection has provided mechanisms that operate within that space to facilitate adaptation to the environment. These mechanisms are more robust than genetics alone in determining the phenotype of each individual organism.