Abstract: Multiple myeloma (MM) is the second most common malignant hematological disorder. Recent advances of bench researches and the development of novel therapeutic agents have led to a dramatic improvement in patients' response and survival. One important milestone is the introduction of proteasome inhibitors (PIs) in the treatmentof MM. As the most selective and reversible PI, bortezomib has shown superior clinical efficacy in the management of MM. Since ixazomib is the first oral PI, it allows for convenient administration in MM patients with good tolerance. The new generation PI, carfilzomib, has a better risk-benefit profile because of improved molecular structure and optimized mechanism of action. In addition, the advantages of PIs in high-risk MM patients render them a superior alternative to standard therapy. In conclusion, with recent advances in the development of PIs and accumulation of supporting evidence, PIs have become the cornerstone of MM treatment. The new generation PIs may provide more optimized alternatives for the individualized treatment of MM patients.