Over the past decade, advances in both gene discovery and ligand-receptor pairing techniques have led to the recognition that systematic pairing of 'orphan' database-derived cytokines and/or cytokine receptors with their cognate partners can lead to a marked acceleration in the elucidation of biological function. The sometimes-restricted tissue distribution of the receptor, coupled with the highly specific bioactivity of the corresponding ligand, can direct investigators rapidly towards regulatory function and site-of-action studies. The power of cytokine-receptor pairing to accelerate the understanding of function will be illustrated, citing several examples of candidate drug discoveries. Several of these discoveries, resulting from cytokine-receptor pairings, are at present advancing towards human clinical evaluation.