The effectiveness of hydroxychloroquine (HCQ) has been increasingly recognized in nearly all major fields of medicine. This ancient but still indispensable drug has a high bioavailability and a very long half-life due to its large volume of distribution. Although HCQ is generally considered a safe and well-tolerated drug, it can sometimes cause mild and reversible reactions that do not require treatment interruption such as gastrointestinal discomfort, photosensitivity and cutaneous findings. However, long-term treatment and high cumulative doses of HCQ may rarely lead to severe adverse reactions (including retinal, neuromuscular, cardiac and auditory toxicities) which are considered serious and require drug discontinuation but unfortunately not always reversible. The interaction of HCQ with other drugs (and vice versa) is also an important clinical issue. It has been emphasized that caution should be used in prescribing medications concurrently with HCQ, such as drugs that prolong QT interval and other arrhythmogenic drugs, drugs known to induce retinal toxicity, insulin or other antidiabetics, digoxin, cyclosporine, drugs used to treat myasthenia gravis and drugs known to lower the convulsive threshold. In this article, the pharmacological properties, clinically significant drug interactions as well as frequent and rare adverse reactions of HCQ have been reviewed in detail.