Hydroxychloroquine (HCQ) is an increasingly popular drug owing to its efficacy, long‑term safety, and a wide range of therapeutic effects. Currently, due to the numerous benefits it provides, the use of the drug goes beyond the treatment of rheumatic and dermatologic diseases. As HCQ shows anti‑inflammatory, immunomodulatory, antiproliferative, and photoprotective action, it has a great potential to be applied also in the treatment of oncologic diseases, multiple sclerosis, diabetes, cardiovascular diseases, or recurrent miscarriages. Nevertheless, antimalarial drugs are still most widely used in the long‑term treatment of systemic rheumatic disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and primary Sjögren syndrome, as they continue to offer satisfactory outcomes. They reduce the need for glucocorticoids and immunosuppressants and increase their effectiveness. In addition, they reduce the risk of possible side effects and complications. This paper presents the latest data on HCQ, its mechanisms of action, its therapeutic potential in current clinical practice as well as future perspectives. It also discusses the correct dosing regimen and long‑term monitoring, with consideration of possible rare complications. Finally, it focuses on the enormous benefits for patients with rheumatic diseases in terms of reducing the disease activity and organ damage, preventing flares and pregnancy‑related complications, and, most importantly, lowering mortality rates in SLE patients.