Akt (also known as protein kinase B) is a key molecule for cell survival and drug resistance in multiple myeloma (MM) cells. Therefore inhibition of Akt activity is the promising therapeutic strategy for treatment of MM. Our preliminary results demonstrate that novel alkyl-lysophospholipid Perifosine induces significant MM cell killing. In this study, I will further examine the anti-MM activity of Perifosine in combination with other conventional and novel agents to provide the basis for combination clinical trials.