Discussion of the positive vs. negative distinction often fails to address whether this distinction refers to symptoms, syndromes, or diseases. Symptoms and syndromes are etiologically nonspecific, while diseases have a specific identifiable pathophysiology or etiology. The positive vs. negative distinction is sometimes discussed as a hypothesis for identifying discrete subtypes of disease within the schizophrenic syndrome. In this overview, the evidence supporting this approach to subtyping is critically reviewed, and modifications of the original form of the hypothesis are proposed.