To examine the role of novel agents such as bortezomib, lenalidomide, and thalidomide as continuous therapy (induction and consolidation/maintenance) in the treatment of newly diagnosed patients with multiple myeloma, we carried out a meta-analysis of randomized-controlled trials. A comprehensive literature search (Medline, Embase, the Cochrane controlled trials register, and the Science Citation Index) was performed. The initial search yielded 849 citations, of which 11 randomized-controlled trials enrolling 4775 patients fulfilled the inclusion criteria. Continuous addition of bortezomib to conventional therapy before and after autologous stem cell transplantation prolonged overall survival significantly: the summary hazard ratio was 0.80, 95% confidence interval [0.64, 0.99] (P=0.04). Continuous therapy with novel agents consistently improved progression-free survival (PFS) compared with therapy with conventional agents alone. For those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.69 [0.56, 0.85] (P<0.001) for continuous thalidomide therapy and 0.47 [0.33, 0.68] (P<0.001) for continuous lenalidomide therapy; for those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.68 [0.59, 0.79] (P<0.001) for continuous thalidomide therapy and 0.72 [0.61, 0.85] (P<0.001) for continuous lenalidomide therapy. In summary, continuous therapy with novel agents improved PFS consistently, and bortezomib may improve the overall survival of patients with newly diagnosed myeloma when it is added to standard transplantation therapy continuously.