The last decade has witnessed an exponential increase in the attempts to demonstrate that adaptive immunity can effectively detect cancer cells and impair their growth in vivo in cancer patients. However, clinical trials of immunotherapy with a broad array of immunisation strategies have depicted a rather disappointing scenario, suggesting that successful control of tumour growth by immunotherapeutic treatments may not be an easy task to achieve. The attention of tumour immunologists has thus been switched to the potential reasons of failure, and extensive efforts are being made in defining the cellular and molecular pathways interfering with the capacity of the immune system to develop powerful immunological reactions against tumour cells. Although many of these pathways have been well characterised in murine models, little and controversial information about their role in determining neoplastic progression in cancer patients is available. This discrepancy at the moment represents one of the major limitations in understanding the obstacles to the in vivo development of protective T cell-mediated immune responses against tumours, and how pharmacological or biological interventions aimed at bypassing tumour escape mechanisms would indeed result in a clinical benefit. The study of the reasons for the failure of the immune system to control tumour growth, which have to be ascribed to highly interconnected phenomena occurring at both tumour and immune levels, could in the near future provide adequate tools to fight cancer by finely tuning the host environment through biological therapies.