Methotrexate (MTX) is an anti-inflammatory, anti-proliferative and immunosuppressant drug largely used worldwide with a well-known efficacy, and it is considered a safe and easy to use agent. MTX was first used in psoriasis, but it represents an effective and safe therapeutic option in a wide range of skin diseases. Despite its common employ, it is still the subject of numerous researches, with the purpose to develop new strategies to increase the manageability and evaluate the efficacy of the treatment, alone and in association with other therapies. Starting up from the official guidelines, we have reviewed the scientific literature, along with our clinical experience, in order to update the uses of MTX in dermatology.