Autoimmune serology has become central in the characterization of many rheumatic conditions and in many cases the presence of an autoantibody (e.g. anti-citrullinated peptide, rheumatoid factor, ANCA, ANA, ENA, anti-phospholipid antibody), may form part of the diagnostic criteria. Increasingly, as pathogenic mechanisms are derived, the role of these autoantibodies is becoming better understood. This chapter covers the key techniques (immunoflourescence, immunodiffusion, ELISA, immunoblotting, immunoprecipitation) used in autoantibody detection as well as the clinico-pathological significance of a positive result.