This review provides an updated overview of the neurophysiological rationale, basic and clinical research literature, and current methods of practice pertaining to clinical neurofeedback. It is based on documented findings, rational theory, and the research and clinical experience of the authors. While considering general issues of physiology, learning principles, and methodology, it focuses on the treatment of epilepsy with sensorimotor rhythm (SMR) training, arguably the best established clinical application of EEG operant conditioning. The basic research literature provides ample data to support a very detailed model of the neural generation of SMR, as well as the most likely candidate mechanism underlying its efficacy in clinical treatment. Further, while more controlled clinical trials would be desirable, a respectable literature supports the clinical utility of this alternative treatment for epilepsy. However, the skilled practice of clinical neurofeedback requires a solid understanding of the neurophysiology underlying EEG oscillation, operant learning principles and mechanisms, as well as an in-depth appreciation of the ins and outs of the various hardware/software equipment options open to the practitioner. It is suggested that the best clinical practice includes the systematic mapping of quantitative multi-electrode EEG measures against a normative database before and after treatment to guide the choice of treatment strategy and document progress towards EEG normalization. We conclude that the research literature reviewed in this article justifies the assertion that neurofeedback treatment of epilepsy/seizure disorders constitutes a well-founded and viable alternative to anticonvulsant pharmacotherapy.