Interferons (IFN) are immunomodulating, antiviral and antiproliferative cytokines for treatment of multiple indications, including cancer, hepatitis, and autoimmune disease. The first IFNs were discovered in 1957, first approved in 1986, and are nowadays listed in the WHO model list of essential medicines. Three classes of IFNs are known; IFN-α2a and IFN-β belonging to type-I IFNs, IFN-γ a type-II IFN approved for some hereditary diseases and IFN-λs, which form the newest class of type-III IFNs. IFN-λs were discovered in the last decade with fascinating yet under discovered pharmaceutical potential. This article reviews available IFN drugs, their field and route of application, while also outlining available and future strategies for bioconjugation to further optimize pharmaceutical and clinical performances of all three available IFN classes.