Vaccination as an approach to control cancer growth and recurrence, also known as active-specific immunotherapy (ASI), has been successful at inducing immune responses, even in patients with advanced or metastatic disease. Clinical responses, as determined by the criteria set for chemotherapy and radiation, have been much more difficult to assess. In general, the effectiveness of ASI in advanced disease is expected to be limited. The lack of toxicity in thousands of vaccinated patients with many different tumor types, and clearly observed, albeit rare, efficacy, support the use of ASI in early disease following resection of the primary tumor or removal of precancerous lesions. This setting will permit a much more rational assessment of the long-term efficacy of ASI, as well as its toxicity. Given that ASI relies on a healthy immune system to be effective, it is also predicted to be more successful when it is employed prior to the use of standard chemotherapy. At the very least, it should be given primary consideration in situations where the role of cytotoxic chemotherapy is equivocal and patients are in need of a nontoxic alternative.