Multiple myeloma (MM) is a plasma cell neoplasm often associated with renal impairment (RI), with myeloma cast nephropathy recognized as the most common cause. While RI is present in over 50% of MM patients at some point in their disease course, it is associated with higher tumor burden, more aggressive disease, diminished quality of life, development of complications and increased mortality. The introduction of novel therapies, including bortezomib, lenalidomide and thalidomide, has revolutionized the management of MM. They are now considered first-line therapies in induction, maintenance and salvage therapy for MM. In addition to their anti-MM effect, they can improve outcome in patients with RI, especially when combined, and bortezomib with dexamethasone may have a renal protective effect. This review focuses on the use of these agents in patients with MM and RI, and evaluates their efficacy, safety, need for dose adjustment and impact on RI.