1993 represents the 100th anniversary of William Coley's first report of tumour regressions induced by immune system activation in response to bacterial toxins. While many subsequent cancer vaccine trials have yielded tantalizing results, active immunotherapy has not yet become an established modality of cancer therapy. Drew Pardoll reviews newer molecular vaccine approaches based on rational immunological principles that have resulted in improved systemic antitumour effects in animal models. Ultimately the genetic definition of tumour-specific antigens will allow the development of targeted antigen-specific vaccines for cancer therapy.