Despite improvements in survival after the introduction of chemo-radiotherapy (CRT) in the treatment of patients with cervical cancer, loco-regional control of this disease continues to be a major problem. The present article reviews current and emerging therapeutic strategies combining CRT with novel molecular agents that specifically target the abnormal tumor microenvironment, with the aim of improving local control and survival in patients with locally advanced cervix cancer. The evidence supporting the biological rational to combine novel non-cytotoxic agents with CRT is strong, and drugs targeting different molecular pathways are currently under clinical development (EGFR inhibitors, COX-2 inhibitors, hypoxia targeted agents, etc). Early pre-clinical and clinical strategies also favor the use of vascular-targeted agents with the aim to normalize the abnormal tumor vasculature, increase tumor oxygenation, and reduce interstitial fluid pressure (IFP). The integration of these novel targeted therapies with CRT in clinical trials is discussed, as well as new and promising biomarkers to test drug activity.