The human skin is constantly exposed to a large number of external pathogens, due to daily contact with the environment. The observation that extensive skin infections are relatively rare suggests the presence of an efficient host defence system at the skin surface. Recent findings indicate the importance of keratinocytes as effectors of innate immunity, but also as regulators of acquired immune responses, inflammation and wound repair. This book considers the current findings regarding the role of keratinocytes in the epidermis with special interest to mechanisms involved in host defence. Finally, the clinical relevance of the functions of keratinocytes in the innate immunity is also discussed.