Proteomics, the large-scale analysis of proteins of a given cell or tissue, is a fast-emerging field in biomedical research. It has become clear that proteomic approaches can assist in unravelling complex disease pathways and can help in the discovery of protein drug targets. The recent flood of proteomic data demonstrates the furious digging in the quest for the so-called 'Holy Grail'. However, at present only a limited number of reports describing proteomic studies in rheumatology have been published. This review highlights some recent advances in the field of proteomic techniques. These new techniques, as well as classic approaches, have potential applications in the field of rheumatology. Some of the proteome studies in rheumatology are directed to the discovery of diagnostic proteins in biological fluids, and others are designed to elucidate the pathophysiology of affected target tissues. As discussed in this review, proteomics is an emerging area in rheumatology and holds great potential in this field. There is little doubt that established and new proteomic tools will lead to landmark discoveries in this field, with applications ranging from diagnostics and therapeutic monitoring to the discovery of new therapeutic targets.