Medical marijuana is becoming widely available to patients in the United States, and with recreational marijuana now legalized in many states, patient interest is on the rise. The endocannabinoid system plays an important role in skin homeostasis in addition to broader effects on neurogenic responses such as pruritus and nociception, inflammation, and immune reactions. Numerous studies of in vitro and animal models have provided insight into the possible mechanisms of cannabinoid modulation on pruritus, with the most evidence behind neuronal modulation of peripheral itch fibers and centrally acting cannabinoid receptors. In addition, human studies, although limited due to differences in the cannabinoids used, disease models, and delivery method, have consistently shown significant reductions in both scratching and symptoms in chronic pruritus. Clinical studies have shown a reduction in pruritus in several dermatologic (atopic dermatitis, psoriasis, asteatotic eczema, prurigo nodularis, and allergic contact dermatitis) and systemic (uremic pruritus and cholestatic pruritus) diseases. These preliminary human studies warrant controlled trials to confirm the benefit of cannabinoids for treatment of pruritus and to standardize treatment regimens and indications. In patients who have refractory chronic pruritus after standard therapies, cannabinoid formulations may be considered as an adjuvant therapy where it is legal.