There are critical maximum temperatures above which irreversible damage occurs in cells and tissues. Exposure to high temperature, referred to as hyperthermia (HT), can result in cell death, tissue damage or even death of the organism. Clinical application of HT as a primary treatment or as an adjuvant to radio-/chemo- therapy of cancer is based on its ability to cause localized tumor tissue damage. Experimental data provide HT with a strong biological rationale. Early clinical experience suggested that HT will become an important modality as an adjuvant to radiotherapy in the treatment of human malignancies, but its application is currently limited to mainly superficial tumors. Its full realization as a treatment modality for cancer therapy awaits further laboratory investigations as well as controlled clinical trials. A better understanding of the biological mechanisms of its action, interaction with chemotherapeutic drugs and radiation damage, role of tumor microenvironment such as oxygen status and pH of tumors, and kinetics of thermotolerance can lead to refinement in its clinical implementation. The present review attempts to analyse the published literature during the last one and half decades.