Context. - Central pathology review (CPR) was initially designed as a quality control measure. The potential of CPR in clinical trials was recognized as early as in the 1960s and quickly became embedded as an integral part of many clinical trials since. Objective. - To review the current experience with CPR in clinical trials, to summarize current developments in virtual microscopy, and to discuss the potential advantages and disadvantages of this technology in the context of CPR. Data Sources. - A PubMed (US National Library of Medicine) search for published studies was conducted, and the relevant articles were reviewed, accompanied by the authors' experience at their practicing institution. Conclusions. - The review of the available literature strongly suggests the growing importance of CPR both in the clinical trial setting as well as in second opinion cases. However, the currently applied approach significantly impedes efficient transfer of slides and patient data. Recent advances in imaging, digital microscopy, and Internet technologies suggest that the CPR process may be dramatically streamlined in the foreseeable future to allow for better diagnosis and quality assurance than ever before. In particular, whole slide imaging may play an important role in this process and result in a substantial reduction of the overall turnaround time required for slide review at the central location. Above all, this new approach may benefit the large clinical trials organized by oncology cooperative groups, since most of those trials involve complicated logistics owing to enrollment of large number of patients at several remotely located participating institutions.