Evidence favoring genetic predisposition to each of the major classes of rheumatic diseases is reviewed, including juvenile-onset rheumatoid arthritis, rheumatic fever, ankylosing spondylitis and other syndromes associated with spondylitis, adult-onset rheumatoid arthritis, gout and pseudogout, and systemic lupus erythematosus. In addition, simply inherited genetic diseases that may present with arthritis are noted for purposes of differential diagnosis. The importance of heterogeneous causes and mechanisms within each major class of disease is emphasized, both for patient care and for clinical investigation.