The specific activation of the immune system to control cancer growth in vivo has been a long‐standing goal in cancer immunology and medical oncology. The identification of tumor‐associated antigens has provided the basis for new concepts in antigen‐specific immunotherapy. The first clinical trials on cancer vaccines were designed to evaluate the toxicity and objectively measurable immunologic effects in relation to clinical developments mostly in patients with metastatic disease. MHC class I‐ and II‐restricted peptide epitopes, antigenic proteins, viral constructs, mini‐genes and whole tumor cells have been used either alone or combined with different cytokines (i.e., IL‐2, IL‐12, GM‐CSF), adjuvants (incomplete Freund's adjuvant, montanide, QS21) or with dendritic cells to induce specific immune responses in vivo. Standardized assay systems to evaluate the immunologic effects of cancer vaccines have been established. Clinical developments during and after vaccination were followed in relation to vaccine‐induced immune responses. Prognostic tumor features, i.e., homogeneity of tumor antigen and MHC class I/II expression and intratumoral cellular infiltrates, have been identified that may help to select patients who are more likely to benefit from antigen‐specific cancer vaccines in the future. © 2003 Wiley‐Liss, Inc.