There has been marked interest in minimally-invasive, image-guided radiofrequency (RF) tumour ablation (i.e. coagulating tumour using short duration heating (<15 min) by directly applying temperatures >50°C via needle electrodes) to treat focal liver, renal, breast, bone and lung tumours. In spite of advances in RF technology and improved understanding of tumour biophysiology that now enable experimental treatment of tumours up to 5 cm, investigators have been unable to achieve complete ablation in many cases, particularly at the tumour margins and adjacent to blood vessels. One strategy for overcoming these limitations has been to take advantage of complementary interactions between RF thermal ablation and chemotherapy, particularly liposomal doxorubicin preparations, to attempt more complete tumour destruction. This paper will review published laboratory investigations demonstrating that this combined treatment paradigm has the unique potential both to potentiate preferential delivery of cytotoxic agents in liposome vehicles and to maximize the completeness of ablation of a treated tumour. New confirmatory data describing increased tumour destruction with RF ablation combined with different liposome preparations, documenting increased lipid peroxidation and expanding on previously published tumour growth studies is presented. Additionally, early clinical data including a randomized, pilot clinical study on 10 patients with primary and metastatic liver tumours, in which a non-optimized combination of RF ablation and IV liposomal doxorubicin (Doxil) increased the volume of tumour destruction 25–30% compared to RF alone, will also be described in detail.