The nature-nurture controversy has historically been defined by extreme positions that ignore the process of evolution and, ironically, the very developmental processes that produce variation in phenotype. In his target article, Myron Hofer describes the impact of the recent emergence of evolutionary-developmental biology (so-called Evo–Devo) and epigenetics for psychoanalytic theory, with particular focus on the importance of early experience in defining stable variation in phenotype. These studies underscore the importance of developmental psychobiology as a field of research that has traditionally emphasized the interactive influences of genetic and environmental forces. However, this G x E perspective raises interesting and very challenging issues for advances in mental health services.