Methotrexate was discovered in the 1940s-1950s and approved by the FDA for treating psoriasis in the 1970s. It works by inhibiting the enzyme dihydrofolate reductase, which is essential for DNA synthesis and cell division. This slows the overactive growth of skin cells in psoriasis. New drugs under development target specific proteins and pathways involved in psoriasis pathogenesis, such as IL-23 (tildrakizumab) and JAK inhibitors (tofacitinib). Biologics and small molecules show promise for more effective treatment of psoriasis.