Our skin is the interface between us and our environment - a flexible barrier that has evolved for protection, immunity, regulation and sensation. Once regarded as inert, we now know that it is a dynamic environment. Skin lipids are crucial to the structure and function of skin. From deep in the hypodermis, through the ceramide-rich epidermis, to the lipids of the skin surface, there are a vast array of different lipids with important roles to play. This review firstly discusses the lipid composition of human skin and secondly, changes that have been found in skin lipid composition in different skin diseases. Further research into skin lipids facilitated by ever-improving methodologies will no doubt generate new knowledge, paving the way for diagnosis, prevention and treatment of skin disorders and diseases.