Type III interferon (IFN) or IFN-lambda is a novel family of class II cytokines that induces antiviral activities both in vitro and in vivo through its own distinctive receptor complex. The recent crystal structure of human IFN-lambda 3 revealed a cytokine with structural similarity to the interleukin-10 family, despite functionally being an IFN. Here, we review the structure of IFN-lambda and its relation to the other members of the class II cytokines. Further, we analyze the structural differences between the tree human isoforms of IFN-lambda and relate this to the observed differences in potency.