Multiple myeloma (MM) is a plasma cell malignancy that can significantly shorten the life expectancy of patients. With the use of drugs such as thalidomide, bortezomib and lenalidomide as first-line therapy, the outcome of MM has improved significantly, but relapse still occurs and the treatment of relapsed MM is indeed a great clinical challenge. Recently, Blood magazine discussed the treatment of relapsing MM in its How I treat series. For asymptomatic relapsed MM, treatment can be delayed appropriately; for already symptomatic, advanced relapsed MM, immediate salvage treatment is necessary. In addition, for patients with multiple relapses, the benefit of retreatment and sequential therapy is clear. For patients with aggressive relapses and those for whom all treatment options have been used, continued treatment until disease progression is recommended. Patients in sustained remission for more than 2 years prior to first autologous stem cell transplantation (ASCT) may benefit from re-treatment with ASCT. In patients with aggressive or associated cytogenetic abnormalities with poor prognosis, allogeneic transplantation should be considered if relapse occurs in the first 2 years after ASCT. Finally, some new drugs are undergoing clinical trials and some patients may be encouraged to participate in this type of study. In the following, we will discuss the treatment of relapsed MM with specific cases. Although the treatment of relapsed MM has progressed considerably in recent years, it is still unsatisfactory and the emergence of new drugs, such as proteasome inhibitors (carfilzomib, ixazomib) or IMiDs (pomalidomide), is to be expected. Data from two recent studies suggest that the histone deacetylase inhibitors (HDAC) vorinostat and pabibistat plus bortezomib may prolong PFS in patients, but toxicity is high and more studies are needed to demonstrate their efficacy. The monoclonal antibodies FRMF7 (elotuzumab) and anti-CD38 (daratumumab, SAR650984), especially when combined with bortezomib/dexamethasone or lenalidomide/dexamethasone, may improve efficacy. More promising is immunotherapy. However, these drugs are still in clinical trials and not really used in the clinic, so let’s wait and see.