IFN-λs or type III IFNs are also known as IL-28/29. This group of cytokines is the latest addition to the family of cytokines that signal through receptors of the class II cytokine receptor family (CRF2). Although IFN-λs and IFN-α/β (type I IFNs) utilize distinct receptor complexes for signaling, type I and type III IFNs activate the same intracellular signaling pathway and many similar biological activities, including the ability to induce antiviral state in cells. Consistent with their antiviral activity, the expression of IFN-λ mRNAs is inducible by viral an infections. Therefore, IFN-λs functionally resemble type I IFNs, supporting their designation as IFNs. However, IFN- λs also share several common features with cytokines of the IL-10 family that includes IL-19, IL-20, IL-22, IL-24 and IL-26. Their genes have a similar intron-exon structure, they share some sequence homology, and most likely they share a similar structural organization. IFN-λs also share a common receptor subunit, IL-10R2, with IL-10, IL- 22 and IL-26. However, the ligand-binding chain, IFN-λR1, is a unique component of the IFN-λ receptor complex. Although the relative importance of the IFN-λs remains to be fully determined, recent experiments demonstrate their strong potential as antiviral and antitumor therapeutics.