Molecular chaperone-based vaccines offer a number of advantages for cancer treatment. We have discussed the deployment of a vaccine prepared by gentle isolation of Hsp70 from tumour dendritic cell fusions (Hsp70 fusion vaccine). The vaccine was highly effective in triggering specific T cell immunity and in the treatment of tumour-bearing mice and the preparation was shown to retain an increased amount of tumour antigens compared to other chaperone-based isolates. This approach has the further advantage that tumour sub-populations could be used to prepare the Hsp70 fusion vaccine. Cellular fusion vaccines were made to specifically target drug-resistant cancer cells and tumour cell populations enriched in ovarian cancer stem cells (CSC). Such vaccines showed enhanced capacity to trigger T cell immunity to these resistant ovarian carcinoma populations. We have discussed the potential of using the cellular and Hsp70 fusion vaccine approaches in therapy of treatment-resistant cancer cells and its deployment in combination with ionising radiation or hyperthermia to enhance the effectiveness of both forms of therapy.