The main route of human immunodeficiency virus-1 (HIV-1) infection is via unprotected sexual intercourse, and therefore, vaginal tissues and male foreskin are viral entry sites. Langerhans cells (LCs) and dendritic cells (DCs) are amongst the first immune cells encountering HIV-1 since these cells line these mucosal tissues. Both LCs and DCs are equipped with specific pattern recognition receptors that not only sense pathogens, but induce specific immune responses against these pathogens. LCs express the C-type lectin receptor langerin, which provides protection against HIV-1 infection. In contrast, DCs express the C-type lectin receptor DC-SIGN, which facilitates capture as well as infection of DCs and subsequent transmission to CD4(+) T cells. This chapter gives an update on immune responses elicited against viruses and sheds a light on different immune mechanisms that are hijacked by HIV-1 to infect the host. HIV-1 infection ultimately leads to the worldwide pandemic acquired immunodeficiency syndrome (AIDS).