Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.