The emergence of clinical positron emission tomography (PET) has enabled a routine and noninvasive assessment of cancer, neurological disorders, and coronary artery disease in humans. Vital to a sustained growth and widespread utilization of this novel methodology, in a clinical environment, is the ready and convenient availability of positron-emitter labeled radiopharmaceuticals. This requirement is aptly met by integrated radiopharmaceutical production systems or electronic radiopharmaceutical generators that comprise of: (1) a low energy, self-shielded negative ion cyclotron; (2) small volume targets for the production of positron emitting precursors; and (3) unit operations based automated synthesizers all under the full control of a personal computer (PC) and entirely operated by a technician. Efforts by both academia and industry during the past 20 years have now led to the inception of such integrated systems that are efficient and highly suitable for the production of multiple doses of numerous radiotracers in clinical settings. The theme of this review is the evolution, over the years, of integrated automated synthesis units from the standpoint of the cyclotrons, targetry, and automated synthesizers. PET radiopharmacies are now making a reality the availability of positron-emitter labeled radiopharmaceuticals for clinical use and are positioning themselves to extend the availability of new PET probes to research environments stimulated by the micro-PET technology. Stand alone automatic synthesis modules also offer a unique avenue to PET radiopharmaceuticals for research. The new Food and Drug Administration (FDA) regulatory environment mandated by the Food and Drug Administration Modernization Act (FDAMA) in 1997, combined with these developments will permit the accessibility of PET radiopharmaceuticals at low cost for a variety of clinical and research applications.