Emerging data support the model that giant cell arteritis (GCA) is an antigen-driven disease. Select helper T cells are recruited to the vascular lesions where they produce a defined pattern of cytokines. At least two functionally distinct populations of macrophages are involved and macrophage activation extends into the compartment of circulating phagocytes. Searches for the antigen may be facilitated through structural analysis of specially activated T lymphocytes in the lesions. In addition to the proposed disease-inducing agent, genetic risk factors are important. One of the genetic elements has been mapped to the HLA-DR region and seems to encode parts of a pocket in the HLA-DR molecule, accommodating side chains of the interacting antigenic peptide. On the molecular level, some but not all pathomechanisms are shared by polymyalgia rheumatica and GCA, indicating that both syndromes form a spectrum of disease.