Topical drug delivery methods are important in the treatment of skin diseases. Drug nanocrystals, which are nanometersized particles of active pharmaceutical ingredients, offer efficient topical delivery with high stability, high drug loading capacity, steady dissolution, and sustained drug release profiles. The use of nanocrystals for the topical delivery of skin disease therapies is currently being evaluated; this review focuses on how nanocrystals facilitate active pharmaceutical ingredient transport across skin barriers, exploring the underlying transportation mechanisms of the nanocrystals and active pharmaceutical ingredient molecules to the dermal and epidermal skin cells. In topical delivery, previous skin treatments, choice of excipients and vehicles, and penetration enhancement strategies critically influence the topical delivery of drug nanocrystals. Various research and applications of drug nanocrystals in skin disease therapy are highlighted in this review, and intellectual property protection for drug nanocrystal formulations, clinical trial data, and products with commercial potential are also discussed.