Methotrexate is a Disease Modifying Anti Rheumatic Drug (DMARD) we used in the treatment of patients with severe fibromyalgia symptoms. We present two case discussions of low dose methotrexate treatment resulting in dramatic relief of widespread body pain in patients diagnosed with fibromyalgia. These patients had been refractory to prior treatment with opioids, NSAIDs, anti-seizure medications, anti-depressant medications, pregabalin and corticosteroids. Our case reports endorse Sota Omoigui’s theory of pain which states that the origin of all pain is inflammation and the inflammatory response. Low dose methotrexate has unique broad spectrum anti-inflammatory activity that is not found in any other medication. The drug may significantly decrease or resolve generalized body pain associated with fibromyalgia. The use of low dose Methotrexate co-administered with folic acid should be considered as an adjunct to pain medication to help decrease and sometimes eliminate pain and improve other symptoms such as fatigue and disability in fibromyalgia. Limiting factors include the ability of patients to tolerate the medication.