Multiple myeloma is a hematological cancer characterized by the clonal proliferation of malignant plasma cells in the bone marrow. That disease has a rather low incidence but displays a high rate of relapse and resistance to conventional therapies. It is therefore necessary to find new therapeutic strategies to overcome this resistance, which is partly attributed to a subpopulation of cells known as cancer stem cells. Withanolides and HDAC6 selective inhibitors were identified as promising compounds in various resistant multiple myeloma models.