Musculoskeletal (MSK) disorders constitute one of the most common clinical presentations to clinical care givers. Within this category of illnesses, systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SjS) and rheumatoid arthritis (RA) are included in the differential diagnosis. A hallmark of SARD is the production of autoantibodies, which are routinely requested as a guide to diagnosis and clinical decision making. The field of serological tests, including the detection of autoantibodies, is complex and often leads to confusion and misunderstanding. When used appropriately, autoantibodies can be a valuable adjunct to the diagnosis, and occasionally therapy and prognosis, of SARD. The role of autoantibody testing and a 'practical' approach to using these tests is the focus of this paper.