A massive amount of information on interferons (IFNs) has been gathered since their original description as antiviral agents in 1957. Human IFNs have now been used clinically for over a decade and their therapeutic efficacy has been well established for some human neoplasias and viral diseases. During these studies, it has also been documented that some of the patients treated with IFNs can develop antibodies to IFNs which can affect their therapeutic efficacy. Here, it is summarized what is currently known on the biological and clinical aspects of these antibodies.