Alterations in barrier function are associated with a number of skin diseases, including xerosis, atopic dermatitis, and psoriasis. Urea, a component of the natural moisturizing factor of the skin, plays an important role in the preservation of skin hydration and integrity. Several studies have investigated the effects of urea in the clinical setting. Here, we summarize the available clinical evidence regarding the effects of urea in the maintenance of healthy skin and management of skin disorders. At lower doses (≤10%), urea‐containing topical formulations act as a skin moisturizer, while at higher concentrations (>10% urea), urea‐based preparations exert a keratolytic action. Urea is also useful in combination therapies with anti‐inflammatory and anti‐fungal drugs, due to its activity as a penetration enhancer.