Extensive research over the past two decades in tumor immunology has shown that immune reactivity to tumor antigens can restrict tumor growth and/or metastasis, especially when tumor burden is low. These observations in experimental models have been translated into clinical studies involving both active and passive forms of immunotherapies. While immune responses to specific tumor antigens can be detected in patients with various types of cancers, responses to any single antigen seldom correlate directly with a clinical response to tumors; however, some clinical regressions of solid tumors have been reported with certain types of cancer vaccines. While passive immunotherapies with antibody to tumor antigens (Avastin®, Herceptin®, Erbitux®, RituxanTM, BexxarTM) are being used to treat selected types of cancers, active immunotherapies may be better suited to potentially elicit a sustained immune response, particularly when administered in an adjuvant setting. This review covers the potential and issues with specific active immunotherapies (SAI) for the treatment of cancer.