<img src=” https://s3.amazonaws.com/production.scholastica/article/24597/large/prnano_662021g_fig_1_060721.jpg?1623108176”> Cannabis-derived compounds and therapies targeting the endocannabinoid system (ECS) are demonstrating benefit for clinical conditions beyond current indications. As our understanding of the ECS in the skin continues to develop, cannabinoids are rapidly showing promise for treating cutaneous pathology. However, unstable pharmacokinetics, bioavailability and skin permeability have been significant constraints on their utility in dermatology. As cannabinoids shift from commercial herbal preparations to prescription drugs, nanosized drug delivery strategies can tackle these physiochemical limitations and allow well-designed clinical trials to establish safety and efficacy. This review summarizes the latest evidence for cannabinoids for skin disease, details the challenges of formulating cannabinoids, and highlights how the success of nanomedicine across therapeutic fields can translate to novel nanocannabinoid therapeutics in dermatology.