For the majority of multiple myeloma (MM) patients, their disease will behave as a chronic disorder with episodes of remission followed by disease progression. Whereas the treatment approach in frontline is rather uniform, treatment at relapse has become more heterogeneous, as therapeutic choices at this stage are driven by many factors including disease characteristics and patient status, but also the previous treatment(s), their therapeutic effect and toxicities, and drug availability. With each treatment course patients also tend to become more vulnerable to hematological and non-hematological toxicities. Therefore, particularly at later relapses where there is no standard of care, the benefits and potential risks of therapeutic decisions should be carefully balanced in each individual patient, to minimize excess toxicities. In this review article, an overview is provided of the currently available treatment options for patients with relapsed or refractory MM.