Importance: The rapid proliferation of laboratory tests related to rheumatology, the recent interest in C-reactive protein as a possible marker for cardiovascular disease risk, and the need to contain the costs of medical care by avoiding unnecessary testing have indicated the need for a review of these tests aimed at general internists. Objective: To provide internists with guidance for when to use specific rheumatology related laboratory tests. Evidence Review: Literature reviews as well as important rheumatology references were appraised in order to give an updated review of the rheumatology laboratory tests included in this review. Findings: Certain rheumatology tests should be employed when an internist suspects a particular autoimmune or connective tissue disease. Conclusions and Relevance: A detailed review of symptoms and examination is of primary importance, while laboratory tests usually serve to support or argue against possible diagnoses.