The human interferon (IFN) system is the best characterized of all animal IFN systems. Until recently it is thought that all IFNs and IFN-related genes and proteins have been discovered. However, in the last three years, the discovery and characterization of IFNs including IFN-epsilon (IFN-epsilon), IFN-kappa (IFN-kappa) and a novel IFN-lambda (IFN-lambda) family, in particular, substantially changed this opinion. In this article, we attempt to review recent developments in the field of interferon discovery and present an overview of current classification of the human IFN system. Characterization of the constituent parts of the human IFN system including ligands, receptors and players involved in the signal transduction pathway are discussed.