Fluoropyrimidines have been the standard care as ajuvant or palliative treatment for malignant gastrointestinal carcinoma over several decades. Their common adverse effects include gastrointestinal effects, myelosuppression, and hand-foot syndrome. Besides, fluoropyrimidines are the second cause of chemotherapy-induced cardiotoxicity and have the different manifestation and machanisms from anthracyclines. With the development of onco-cardiology, increasing concern is raised on fluoropyrimidine-induced cardiotoxicity. This review addresses the epidemiology, clinical manifestation, and proposed mechanisms; and also highlights the diagnosis, monitoring and management of fluoropyrimidine-induced cardiotoxicity.