Nanotechnology and nanomedicine provide a platform for advanced therapeutic strategies for dermal and transdermal drug delivery. The focus of this review is on the current state-of-art in lipid-based nanotechnology and nanomedicine for (trans)dermal drug therapy. Drug delivery nanosystems based on the (phospho)lipid constituents are characterized and compared, with the emphasis on their ability to assure the controlled drug release to the skin and skin appendages, drug targeting and safety. Different types of liposomes, biphasic vesicles, particulate lipid-based nanosystems and micro- and nano-emulsions are discussed in more details. Extensive research in preclinical studies has shown that numerous parameters including the composition, size, surface properties and their combinations affect the deposition and/or penetration of carrier-associated drug into/through the skin, and consequently determine the therapeutic effect. The superiority of the most promising nanopharmaceuticals has been confirmed in clinical studies. We have selected several common skin disorders and provided overview over promises of nanodermatology in antimicrobial skin therapy, anti-acne treatment, skin oncology, gene delivery and vaccines. We addressed the potential toxicity and irritation issues and provided an overview of registered lipid-based products.