Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) getting into contact with the virus it has been shown that the processing of viral antigens and the differentiation of anti-viral CTLs is mediated by migratory CD103(+) dermal DCs and CD8α(+) lymph node-resident DCs. In vivo regulatory T-cells (Tregs) are implicated in the regulation of anti-viral immunity and we have shown that signaling via the receptor activator of NF-κB (RANK) and its ligand RANKL mediates the peripheral expansion of Tregs. However, in addition to expanding Tregs RANK-RANKL interactions are involved in the control of anti-microbial immunity by up-regulating the priming of CD4(+) effector T-cells in LCMV infection or the generation of parasite-specific CD8(+) T-cells in Trypanosoma cruzi infection. Here, we demonstrate that cutaneous RANK-RANKL signaling is critical for the induction of CD8-mediated anti-viral immune responses during HSV-1 infection of the skin by preventing virus-induced LC apoptosis, improving antigen-transport to regional lymph nodes and increasing the CTL priming capacity of lymph node DCs.Journal of Investigative Dermatology accepted article preview online, 15 June 2015. doi:10.1038/jid.2015.225.