The unique immunomodulatory properties of hydroxychloroquine (HCQ) have attracted considerable interest beyond its use for malaria and rheumatological diseases, including a variety of dermatological conditions. Over recent years, especially after the coronavirus disease 2019 (COVID-19) pandemic, the prescription of HCQ has also significantly expanded, sometimes inappropriately, thus posing additional challenges on its optimal use, due to emerging safety issues. In this review, we provide dermatologists with the latest advancements on selected clinically relevant toxicities, namely retinopathy, pro-arrhythmia, cutaneous reactions, and neuropsychiatric effects. It is hoped this update can assist dermatologists to identify high-risk patients for tailored monitoring, screening, and risk minimization strategies, thus supporting safer HCQ prescribing.