Proteomics technologies are emerging as a useful tool in the identification of disease biomarkers, and in defining and characterising both normal physiological and disease processes. Many cellular changes in protein expression in response to an external stimulus or mutation can only be characterised at the proteome level. In these cases protein expression is often controlled by altered rates of translation and/or degradation, making proteomics an important tool in the analysis of biological systems. In the leukaemias, post-translational modification of proteins (e.g. phosphorylation, acetylation) plays a key role in the molecular pathology of the disease: such modifications can now be detected with novel proteomic methods. In a clinical setting, serum remains a relatively un-mined source of information for prognosis and response to therapy. This protein rich fluid represents an opportunity for proteomics research to benefit hematologists and others. In this review, we discuss the technologies available for the study of the proteome that offer realistic opportunities in haematology.