Cancer vaccines have the potential to provide a nontoxic treatment for the prevention of cancer recurrence in the adjuvant setting. Many cancer vaccines have been tested in multiple phase III trials with minimal success. However, through these failed clinical trials, we have learned that the ideal setting for vaccine therapy is the adjuvant setting. Also, we have learned important lessons about patient selection to maximize the probability of success. This article will highlight some of the successes, our trial results in the adjuvant setting, and future directions.