Abstract: Multiple myeloma (MM) is a malignant plasma cell clonal disease and the second most common malignant tumor of the blood system, accounting for approximately 1% of all tumor diseases and 13% of hematologic cancers. In recent years, its incidence has shown an upward trend. The development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and autologous hematopoietic stem cell transplantation (auto-HSCT) has greatly improved the efficacy and prognosis of patients with myeloma. Among these, the development and clinical application of PIs represents a major milestone. However, long-term clinical experiencehas revealed that patients with MM who used PIs may develop new heart diseases, such as hypertension, cardiac insufficiency, arrhythmia, and ischemic heart disease, especially those who used cafilzomib. The use of PIs increases the probability of adverse cardiovascular events (CVAEs). Owing to the significant heterogeneity in the definition of cardiotoxic endpoints, the exclusion of high-risk patients in clinical trials and the detection and treatment of PI-related CVAEs vary. Therefore, the lack of sufficient evidence-based medical data hinders the standardized diagnosis and treatment of PI-related CVAEs. This review summarizes the relevant mechanisms and response measures of cardiovascular diseases induced by PIs.