Studies in patients with psoriasis and rheumatoid arthritis treated with methotrexate suggest that functional single nucleotide polymorphisms (SNPs) in genes relevant to methotrexate metabolism may influence both efficacy and toxicity of the drug.1–12 Such studies have focused on isolated functional polymorphisms in only a few genes relevant to methotrexate metabolism and results have been variable, especially in the most investigated gene methylenetetrahydrofolate reductase (MTHFR); (Table 1). The gene discussed is MTHFR; the disease is rheumatoid arthritis.