Intraoperative radiation therapy (IORT) has been used for over 30 years in Asia, Europe and America as a supplementary activity in the treatment of cancer patients with promising results. Modern IORT is carried out with electron beams (IOERT) produced by a linear accelerator generally used for external beam irradiation (EBRT) or a specialized mobile electron accelerator. HDR brachytherapy (HDR-IORT) has also been applied on selected locations. Retrospective analysis of clinical experiences in cancer sites such as operable pancreatic tumour, locally advanced/recurrent rectal cancer, head and neck carcinomas, sarcomas and cervical cancer are consistent with local tumour control promotion compared to similar clinical experiences without IORT. New emerging indications such as the treatment of breast cancer are presented. The IORT component of the therapeutical approach allows intensification of the total radiation dose without additional exposure of healthy tissues and improves dose-deposit homogeneity and precision. Results of the application of IORT on selected disease sites are presented with an analysis on future possibilities. To improve the methodology, clinical trials are required with multivariate analysis including patient, tumour and treatment characteristics, prospective evaluation of early and late toxicity, patterns of tumour recurrence and overall patient outcome.