Conceptualizations of the liability for schizophrenia help guide the development of research protocols, which, in turn, provide empirical confirmations or disconfirmations of the conceptualization's tenets. This paper focuses on a conception of liability and its relationships to genetic adolescent high-risk studies. Specifically, the derivation and nature of a proposed multidimensional syndrome of liability to schizophrenia ("schizotaxia") are outlined, followed by a representative review of features reported in previous high-risk studies that may be related to schizotaxia, and a perspective on future high-risk investigations. Overall, genetic high-risk studies generally confirm the concept of liability in the offspring of parents with schizophrenia, as expressed by deficits or abnormalities in multiple dimensions. It is concluded that high-risk studies on the liability to schizophrenia provide an important tool with which to explore the etiology and development of schizophrenia, in part by contributing to the identification and validation of specific liability syndromes.