Small cell lung cancer (SCLC) is a lethal disease with a very restricted armamentarium of active treatments. In the new era of targeted therapies, several attempts based on the combination of chemotherapy with new compounds has been made but with a low rate of success. The idea of using the new targeted therapies as maintenance treatment after their combination with chemotherapy has been pursued. The aim of the present study was to analyze the available clinical data regarding the effect of the targeted agents as maintenance therapy on survival in patients with SCLC. A literature-based meta-analysis of randomized controlled trials, in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines, was performed. PubMed, the Cochrane Library, and a search of abstracts presented at American Society of Clinical Oncology meetings were searched for relevant studies. The primary outcome was overall survival (OS). Nine studies, with a total of 1385 patients, were included. The pooled analysis revealed that the new targeted therapies did not improve survival compared with the control arm (placebo, hazard ratio, 1.02; 95% confidence interval, 0.91-1.15; P = .69). However, a small advantage in the 1-year OS rate (risk ratio, 1.21; 95% confidence interval, 0.9-1.63; P = .21) was observed. Maintenance with targeted therapies failed to improve the survival of patients with SCLC with an increased rate of toxicity. The detected survival advantage suggests that perhaps the maintenance approach could be used to increase the 1-year OS rate. However, this finding requires confirmation in further studies, perhaps of patients selected according to their tumor biologic profile.