Nanocrystals, nanosized form of active pharmaceutical ingredients (APIs), have emerged as a promising strategy to overcome the formidable barrier of the stratum corneum and enhance both transdermal and follicular drug delivery. As matrix-free systems, nanocrystals offer exceptionally high drug loading, increased saturation solubility, rapid dissolution, and strong bioadhesion, enabling improved skin penetration, retention, and bioavailability of poorly water-soluble drugs. Their capacity to accumulate within hair follicles allows them to act as drug reservoirs, supporting sustained release and targeted therapy for conditions such as acne, psoriasis, eczema, leishmaniasis, skin cancer, and alopecia. This chapter discusses the application of nanocrystals in transdermal drug delivery and hair follicle targeting, while also highlighting key factors, including particle size, shape, surface charge, stabilisers, and delivery vehicles, which critically influence their performance.