The recognized clinical spectrum of disease associated with HIV infection is rapidly expanding and now includes a variety of rheumatic syndromes. The laboratory features of HIV infection closely resemble those found in many connective tissue diseases and thus alter the predictive value of these tests in the evaluation of both types of conditions. In addition to the laboratory similarities, there are also increasing numbers of clinical reports of HIV-infected individuals who develop syndromes either resembling classic idiopathic rheumatic diseases such as SS, polymyositis, or SLE, or newly recognized illnesses that fall under the clinical domain of the rheumatologist (ie, HIV-associated vasculitis and arthritis). It is vital that clinicians recognize these new illnesses because there are important differences in prognosis and management between these and their idiopathic counterparts. Research is urgently needed for better definition of these syndromes and their pathogenesis, natural history, and optimal therapies.