The recent availability of novel agents has substantially improved the outcomes of patients with Multiple Myeloma (MM). Achieving the deepest level of complete response and maintaining a sustained remission are important steps towards MM cure. To achieve this goal, consolidation and maintenance therapies are currently incorporated into the modern therapeutic paradigm. The excellent activity shown by new drugs has led to their investigational use as maintenance therapy. However, despite promising results of continuous treatment with the novel agents, consensus regarding maintenance therapy still lacks. This review will focus on maintenance therapy, offering an overview of the different strategies available in MM. The issue of continuous treatment in the light of new biological discoveries, including intra-clonal heterogeneity, will also be addressed.