Fibromyalgia (FM) is a common syndrome characterised by widespread pain and at least 11/18 painful tender points that requires multimodal pharmacological treatment also combined with non-pharmacological therapy. Various drugs currently are available to control the complex and different symptoms reported by patients. Only three drugs (duloxetine, milnacipram, pregabalin) are approved by the American Food and Drug Administration (FDA) and none by the European Medicines Agency (EMEA), consequently, off-label use is habitual in Europe. Most of the drugs improve only one or two symptoms; no drug capable of overall symptom control is yet available. Furthermore, different classes of drugs with different mechanisms of action are used off-label, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), opioids, non-steroidal anti-inflammatory drugs (NSAIDs), growth hormone, corticosteroids and sedative hypnotics. As no single drug fully manages FM symptoms, multicomponent therapy should be used from the beginning. Various pharmacological treatments have been used to treat FM with inconclusive results, and gradually increasing low doses is suggested in order to maximise efficacy. The best treatment should be individualised and combined with patient education and non-pharmacological therapy.