Type I interferons, constituting IFN-alpha and IFN-beta, were initially described for their ability to interfere with viral replication. IFN-alpha was the first cytokine to be cloned and used successfully as a therapeutic cytokine, although its mechanism of action remained largely elusive. Evidence gathered over the last few years shed light on the molecular effects of IFN-alpha, especially its interaction with the cytokine cascade. Recently, the principle source of IFN-alpha could be identified as the precursor of type 2 dendritic cells, and IFN-alpha has been identified as the cytokine linking innate with adaptive immunity via its interaction with dendritic cells.