Psoriasis is considered to be a polygenetically influenced, immune-mediated, organ-specific disease of dysregulated inflammation that is triggered by environmental factors such as infections, medications, and physical and/or emotional stress. It is recognised as one of the most prevalent skin diseases, affecting 2% to 3% of Caucasian populations. Major advances in understanding of disease pathogenesis indicate that patients with psoriasis have an increased risk of comorbidities such as metabolic syndrome and cardiovascular disease. A wide range of systemic drugs have been developed in recent years for treatment of psoriasis and comorbidities. Low-dose methotrexate (MTX) is one of the classical agents and is still one of the most frequently used systemic treatments for psoriasis worldwide. Low-dose MTX is also effective in treatment of psoriatic arthritis. The mechanism of action is not fully understood, but MTX is suggested to act primarily as an anti-inflammatory and immunosuppressant drug. A favourable efficacy and safety profile has been established for MTX in a large number of clinical trials, as well as in common practice. This review summarises the nature of the disease and our present knowledge about MTX in the treatment of psoriasis, including combination therapies.