The recent explosion in knowledge in the neurosciences has heightened both the expectation of significant progress in understanding the underlying mechanisms involved in the psychoses as well as frustration over the failure of such progress to occur. As biological sophistication increases, it contrasts with the obsolescence of our nosological tools, which, through their influence upon research strategy, constitute a potential obstacle to progress. Currently dominant nosological paradigms are heavily based upon assumptions concerning the links between pathophysiology and symptoms, and between symptoms and the more distal consequences of disease. This review seeks to illustrate that the linkages between disease and its consequences are in fact much looser and more plastic than acknowledged by existing paradigms, which are constrained by tradition. Since faulty assumptions concerning these linkages are so fundamental to the current nosology, it is argued that major reform is necessary. While this can be justified on research grounds alone, there are also compelling clinical reasons why reform of this kind is important and overdue.