Antigen-specific T cells are thought to drive the inflammatory response in a number of rheumatic diseases including RA and the spondyloarthropathies. T cells recognise specific combinations of antigenic peptides bound to of HLA molecules, and subsequently proliferate and perform effector functions including cytokine secretion. Techniques have been developed to detect these T cells (usually ex vivo or in vitro), based upon their antigenic specificity, their function, and their clonality. Some techniques combine these attributes. Recently fluorescent-labelled multimers (usually tetramers) of synthetic HLA/peptide combinations have been used to stain T cells of defined antigen specificity. The use of HLA /peptide tetramers has greatly increased our understanding of the role of T cells in viral infections and given some insight into rheumatic diseases. Other techniques have been developed that detect cytokines produced in response to specific antigens (i.e. detecting function), or that detect populations of T cells carrying the same or related T cell receptors. Our ability to detect antigen-specific T cells has important implications for our understanding of disease pathogenesis, and for monitoring disease progress. These methodologies also offer therapeutic potential.