Current systems of classification of endogenous psychoses, the APA's Diagnostic and Statistical Manual and the International Classification of Diseases in particular, aim at a synthesis of Kraepelin's prognosis-orientated diagnostic scheme with the symptomatological approach as established by Eugen Bleuler and Kurt Schneider. The restriction to few diagnostic entities has remained unchanged to the present day and appeared at first to be confirmed and validated by modern pharmaco-psychiatry. Kraepelin's dichotomy has failed to make a major contribution to the etiologic clarification of endogenous psychoses. New diagnostic concepts beyond those currently applied in clinical psychiatry and biological psychiatric research must therefore be considered and should lead towards a more differentiated approach to psycho-pathological phenomena. Karl Leonhard's classification of endogenous psychoses which rests upon the pioneer work of Carl Wernicke and Karl Kleist is part of a tradition in psychopathology emphasizing the interface of biology and psychopathology. It might provide a basis for future empirical research in biological psychiatry and pharmacopsychiatry.