Circulating naı̈ve T cells do not recognize tumor-associated antigens (TAA) directly but need to interact with dendritic cells that have had the chance to process TAA for presentation to T cells. According to recent evidence, TAA from tumor cells circulating in the blood reach the spleen and bone marrow, where resident dendritic cells can process and cross-present them to prime T cells. This in turn leads to the generation of effector and memory cells, which can either destroy tumor cells or control them in a state of tumor dormancy. For therapeutic purposes, memory T cells can be boosted by the application of tumor vaccines that express TAA, together with danger signals. Immunization of cancer patients with such a tumor vaccine has resulted in improved survival in several Phase II studies. It is proposed that such immunization leads to long-lasting protective anti-tumor memory.