Random mutations in cancer cells generate unique antigens in each patient's tumour, warranting a personalized treatment approach. Autologous heat shock protein-peptide complexes (HSPPCs) produced from a patient's cancer tissue provide such a personalized approach without the need to identify the unique antigens contained in the individual vaccine. HSPPCs elicit adaptive and innate immune responses and have been tested in a variety of animal models and different human cancers. Currently, there are more than 150 medical centres worldwide enrolling cancer patients in randomized, controlled Phase III clinical trials testing autologous HSPPCs vaccines. This review summarizes the key steps involved in the translation of HSPPCs--from basic science to advanced clinical investigation.