Methotrexate (MTX) has remained the backbone of the treatment for moderate to severe psoriasis ever since its first use nearly half a century ago. Over the years, its high efficacy, low cost, relative ease of administration and usefulness in concomitant psoriatic arthritis have contributed in making MTX the drug of choice in managing severe psoriasis. Although the majority of patients achieve remission of disease activity with MTX, a significant proportion may experience mild and transient adverse effects. From time to time, various guidelines on the use of MTX have correctly and adequately stressed the need for strict monitoring of haematological and hepatic adverse events. Over the years, the safe total cumulative dose of MTX (above which the risk of developing liver fibrosis is significantly increased) has been raised. Simultaneously, there has been an increased emphasis on developing noninvasive tests such as scanning and serum biomarker assays for detecting early liver fibrosis, in order to obviate the need for liver biopsy. However, the recent discovery and subsequent proliferating use of biological response modifiers has gradually shifted the focus away from MTX, despite it still being the most commonly prescribed drug for psoriasis worldwide. The aim of this review is to present a detailed account of MTX therapy and its use in psoriasis, along with its current relevance in disease management in the evolving era of biological drugs.