There is a renewed enthusiasm for therapeutic vaccination as a viable treatment for patients with cancer. Early tumor vaccines were comprised of whole tumor cells, fragments of tumor cells, or protein lysate from tumor cells. Limited results with these approaches led investigators to begin developing the next generation of cancer vaccines based on defined tumor-associated antigens (TAAs). Defining and characterizing TAAs for human cancer, development of new approaches for identifying TAAs, and novel strategies to deliver the antigens as potent therapeutic vaccines have all been the focus of intense research in the past decade and will continue to be the focus for decades to come.