This chapter examines the evidence from family or genetic high-risk studies in schizophrenia, an example of a highly heritable, complex neuropsychiatric disorder for which the aetiology and pathophysiology remain elusive. It discusses a rationale for using family/genetic high-risk studies and the concept of endophenotypes. Emphasising applications in schizophrenia research, Gottesman and Gould provide compelling evidence to suggest that further study and identification of endophenotypes hold tremendous promise for clarifying the aetiology and pathophysiology of schizophrenia, and improving its treatment. In addition to the endophenotypes, measurement of olfactory functioning is independent of diagnosis and hence provides a feasible approach, both practically and economically, for assessing abnormal brain function and genetic vulnerability to schizophrenia. Continued investigations of the olfactory system and related abnormalities, and particularly its role as an endophenotype, may aid in unravelling the mysteries of the molecular and genetic underpinnings of schizophrenia and other complex neuropsychiatric diseases.