Introduction: The treatment of fibromyalgia is evolving, and more and more drugs are available on the market. Objective: To verify the response, tolerability, and adverse events of the use of psychotropic drugs in the treatment of fibromyalgia. Methods: A systematic review of articles on fibromyalgia and psychotropic medications were carried out, indexed in the MEDLINE database (PUBMED) with the MeSH terms: “fibromyalgia”, “psychotropic drugs,” and “treatment outcome”. Of the 89 studies identified, 23 met the eligibility criteria. Results: It has been seen that some classes of psychotropic medications have significantly improved patients' painful episodes, which have an important positive impact on quality of life. Thus, it was realized that the pharmacological treatment of psychiatric disorders associated with fibromyalgia improves the condition of the patient's acceptance of the disease. Most medications had a good impact on the patient's quality of life without major side effects. It is known that adverse events are proportional to the dose of psychotropics, so for each patient, it is necessary to individualize the conduct. Conclusion: Antidepressants were the best-tolerated drug class, but antipsychotics, anticonvulsants, and other more recent drugs such as agomelatine were part of the study of the main drugs used in clinical practice.