Both the expression and biology of the tumor-associated antigen (TAA) 5T4 suggest that it is an effective target for cancer immunotherapy. This paper reviews the development of a novel immunotherapeutic vaccine comprising the highly attenuated modified vaccinia ankara virus encoding 5T4 (MVA-5T4, aka TroVax). Preclinical studies have demonstrated that MVA-5T4 is safe and highly effective in both the prophylactic and active treatment of syngeneic murine tumor models. More importantly, > 700 doses of MVA-5T4 have been administered to > 200 patients to date. Reported results from clinical trials in metastatic colorectal, metastatic renal and hormone-refractory prostate cancer patients demonstrate that MVA-5T4 is safe and highly immunogenic, both as a monotherapy and in combination with standard-of-care therapies including irinotecan, oxaliplatin, IFN-alpha and IL-2. These studies demonstrate that MVA-5T4 induces potent and sustained immune responses in approximately 95% of tested patients. In addition, post-hoc analyses of these studies have noted a correlation between anti-5T4 immune responses and indicators of clinical benefit. With its minimal side effects and demonstrated ability to produce strong immune responses in patient populations, MVA-5T4 is a promising addition to the cancer therapy arsenal.