Intraoperative probes have been employed to assist in the detection and removal of tumors for more than 50 years. For a period of about 40 years, essentially every detector type that could be miniaturized had been tested or at least suggested for use as an intraoperative probe. These detectors included basic Geiger-Müller (GM) tubes, scintillation detectors, and even state-of-the-art solid state detectors. The radiopharmaceuticals have progressed from (32)PO(4)(-) injections for brain tumors to sophisticated monoclonal antibodies labeled with iodine-125 for colorectal cancers. The early work was mostly anecdotal, primarily interdisciplinary collaborations between surgeons and physical scientists. These collaborations produced a few publications, but never seemed to result in an ongoing clinical practice. In the mid 1980s, several companies offered basic gamma-detecting intraoperative probes as products. This led to the rapid development of radioimmunoguided surgery (RIGS) and sentinel node detection as regularly practiced procedures to assist in the diagnosis and treatment of cancer. In recent years intraoperative imaging probes have been developed. These devices add the ability to see the details of the detected activity, giving the potential of using the technique in a low-contrast environment. Intraoperative probes are now established as clinical devices, they have a commercial infrastructure to support their continued use, and there is ongoing research, both commercial and academic, that would seem to ensure continued progress and renewed interest in this slowly developing field.