Papadopoulos et al. recently reported the discovery of a diagnostic serum proteomic signature for human African trypanosomiasis (HAT), using a combination of surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry and data-mining algorithms. This novel approach, coupled with biochemical characterization of the proteins that contribute to the signature, provides powerful new tools for the development of improved diagnostic tests, disease staging and identification of potential novel drug targets in HAT.