James Joyce, unanimously considered one of the greatest novelists of the 20th century, suffered from several diseases. A series of adverse circumstances progressively deteriorated his health, already precarious because of his very disorderly life habits. Aim of the present study is to summarize the various organic diseases Joyce suffered during his lifetime, as long as the main diagnostic conclusions found in scientific literature. Severe eye problems, caused by recurrent iritis attacks even complicated by glaucoma and cataracts, led him almost to blindness. Undernourishment and irregular eating, great anxiety and alcohol abuse were the major causes of the peptic ulcer which tortured him for many years, causing his final death. To these conditions should also be added dental caries, venereal diseases and recurrent polyarthritis. The hypothesis according which Joyce suffered from neurosyphilis is still debated and should be sufficiently demonstrated, whereas a spondyloarthropathy, either Reiter's syndrome or ankylosing spondylitis, appears more likely. Therapies against these diseases, easily treated today, did not result efficient because of his poor compliance, as well as the state of the art of medical science during his lifetime. A detailed paleopathologic study of Joyce's human remains could allow to solve the diagnostic doubts concerning his main disease.