Several clinical trials carried out during the last decade clearly show that concomitant radiotherapy and chemotherapy significantly improves local control in a variety of advanced solid tumours. In most of these trials, cisplatin alone or in combination with other drugs has been used. This has led to improved survival rates in head and neck, lung and cervical cancer. The interaction of radiotherapy with chemotherapy for these solid tumours appears to be schedule-dependent, as no such an improvement was observed with neo-adjuvant chemotherapy followed by radiotherapy in eight out of nine clinical trials in cervical cancer. A major advantage of this combined modality treatment is organ preservation possible for patients with advanced larynx or anal cancer. Major further improvement can be expected from the design and exploration of drugs that influence the pathways leading to cell death after irradiation. Examples include topoisomerase 1 (topo1) inhibitors, alkyl-lysophospholipids, epidermal growth factor receptor (EGFR) receptor inhibitors.