One of Irving I. Gottesman's many contributions to behavior genetics, and part of his enduring legacy, was his introduction of the term ‘endophenotype’ to the field of psychiatry. Gottesman argued that focusing on endophenotypes, rather than complex heterogeneous clinical diagnoses, could help elucidate disease etiology. Although a different strategy for gene identification ultimately proved successful (that of amassing extremely large sample sizes in order to overcome the ‘noise’ of heterogeneity and have sufficient power to find genes of very small effect), the endophenotype concept continues to make a meaningful contribution to the field. The endophenotype concept forced the field to move beyond a simple disease model of finding genes ‘for’ psychiatric outcomes, and reminded us that genes are quite distal from complex behavioral outcomes and disorders. Endophenotypes called our attention to the steps along that pathway. In that process, the concept of endophenotypes evolved and expanded to include discussion of the role that other intermediary traits and psychological processes play in the development and genetic etiology of psychiatric and substance use disorders. As large-scale consortia continues to identify genes and generate genome-wide polygenic scores that are associated with behavioral outcomes, the next important step will be to characterize the pathways and mechanisms by which genetic risk unfolds. This essential step of mapping risk from genes to behavior is an evolution that follows naturally from the endophenotype concept, and could ultimately translate into improved prevention and intervention for individuals who are pre-disposed to mental health challenges.