Emil Kraepelin (1856-1926) was an influential figure in the history of psychiatry as a clinical science. This paper, after briefly presenting his biography, discusses the conceptual foundations of his concept of mental illness and follows this line of thought through to late 20th-century "Neo-Kraepelinianism," including recent criticism, particularly of the nosological dichotomy of endogenous psychoses. Throughout his professional life, Kraepelin put emphasis on establishing psychiatry as a clinical science with a strong empirical background. He preferred pragmatic attitudes and arguments, thus underestimating the philosophical presuppositions of his work. As for nosology, his central hypothesis is the existence and scientific accessibility of "natural disease entities" ("natürliche Krankheitseinheiten") in psychiatry. Notwithstanding contemporary criticism that he commented upon, this concept stayed at the very center of Kraepelin's thinking, and therefore profoundly shaped his clinical nosology.