Fibromyalgia is a clinical syndrome of chronic widespread pain and reduced pain thresholds to palpation. The pathophysiology remains unknown, but there is increasing evidence that peripheral and central sensitization cause an amplification of sensory impulses that may alter pain perception in fibromyalgia patients. Interventions to treat fibromyalgia should aim at different targets simultaneously in order to reduce peripheral and central sensitization. There are both pharmacologic and non-pharmacologic approaches with evidence for effectiveness in the treatment of fibromyalgia and its associated symptoms. Evidence from randomized trials and meta-analyses shows that partial and short-term improvements in fibromyalgia symptoms can be achieved with low doses of antidepressants and with physical activity such as aerobic and strengthening exercises. A multidimensional approach which emphasizes education and integration of exercise and cognitive behavior therapy improves quality of life and reduces pain, fatigue and depressive symptoms when measured on a short term basis. More recently, trials have shown the neuromodulators gabapentin and pregabalin to be effective in reducing pain and improving quality of sleep in fibromyalgia. In addition, small trials of noninvasive brain stimulation have also shown benefits in reducing pain in fibromyalgia. It is essential to keep in mind that some important clinical conditions can mimic and overlap with fibromyalgia and should always be ruled out by a complete history, physical examination and appropriate laboratory testing.