Double refractory Multiple myeloma is defined as disease resistant to both bortezomib and lenalidomide. It is particularly difficult phase of the disease to treat with median survival of 8-9 months and limited treatment options. But scenario has changed with the availability of newer proteasome inhibitor (carfilzomib , ixazomib), 3rd generation immunomodulator drug (pomalidomide) and targeted therapy (Daratumumab, elotuzumab). Pomalidomide and dexamethasone has PFS of 4 months and median survival of around 12 months in this setting based on results of MM-02, MM-03 and MM-010 trial. Single agent Daratumumab has PFS 0f 4 months and median survival close to 18 months based on result of SIRIUS Trial with approximately 10% reporting VGPR or better. Single agent carfilzomib in 20/27 schedule used in PX-171-003-A1 study demonstrated median survival of 12 months in double refractory patients. Toxicity profile , route of administration, comorbid illness and patient preference are some of the factors that help in drug selection.