Recombinant alfa interferons (IFN-αs) are approved worldwide for the treatment of a variety of cancers and diseases of virologic origin. A series of recent advances in the molecular characterization of recombinant IFN-αs have allowed the determination of the three-dimensional IFN-α(2b) structure by high-resolution x-ray crystallography. We review here recent developments in our understanding of the molecular and physicochemical properties of recombinant IFN-α, including our current state of knowledge of the IFN-α gene family and the multiple species of human leukocyte IFN. Based on the reported three-dimensional structure of IFN-α(2b) we propose a molecular model for the IFN-α(2b) receptor complex and predict models for the naturally occurring subtypes IFN-α1 and lFN-α8, as well as the synthetic, non-naturally occurring consensus IFN. Such models provide molecular insights into the mechanism of action of IFN-α.