Langerhans cells (LC) are antigen presenting cells of the epidermis originated from bone marrow progenitors that arrive into the epidermis through the blood vessels LC are also referred to as dendritic cells. In the presence of antigens LC become activated and migrate from the skin to the lymph nodes where they induce T cells responses, therefore, LC function as sentinels of the epidermis and constitute, in part the Skin Immune System (SIS). LC have been implicated in the pathogenesis and pathophysiology of diverse diseases such as atopic dermatitis, alopecia areata, human immunodeficiency virus infection (HIV) and melanoma, among others. The aim of this review is to draw the attention of pharmacologists towards LC as targets for drug action and drug development due to their immunesurveillance function. LC modulate the SIS as an endogenous mechanism of defense against many infectious agents, xenobiotics, and for the treatment of cancer, infections, and autoimmune diseases. A review of the literature on LC is presented here giving emphasis to LC cell cycle and cellular and molecular characteristics, LC possible role in human pathologies, and LC therapeutic potential.