Emil Kraepelin fundamentally shaped our current psychiatric nosology. Although much has been written about his diagnostic formulations, less is known about his views on the fundamental nature of psychiatric illness and the goals of psychiatric nosology. We focus on his writings from 1896 to 1903 but also review his inaugural lecture in Dorpat in 1887 and his last two papers, published in 1919–1920. Kraepelin hoped for a ‘ natural ’ classification of psychiatric illness but realized that the level of etiologic knowledge required to undergird this effort was not feasible in his own lifetime. This did not stop him, however, from developing a pragmatic approach based on his clinical method of careful description with detailed follow-up, coupled with the available fallible tools of pathological anatomy and, by 1919, genetics and biochemistry. Kraepelin saw psychiatric disorders as multifactorial, arising from the difficult to untangle action and interaction of internal and external causes. He was aware of the problem of defining the boundaries of illness and health but knew this was not unique to psychiatry. Contrary to his stereotype, he was sensitive to the importance of personality factors in psychiatric illness and advocated for their investigation. He also recognized the limitations of his ‘ clinical method' and was especially critical of classifications based on single prominent symptoms. Ultimately, Kraepelin was a skeptical realist when it came to psychiatric nosology. His goal of developing a consistent ‘ natural ’ classification of the major mental disorders has yet to be attained, but his ‘ research agenda' remains central to psychiatry to the present day.