The game of chess has provided a proper domain to study central psychophysiological mechanisms underlying basic psychological processes such as stress, emotion, or decision-making. This chapter describes the studies about the psychophysiology and brain functioning of chess players mostly involving the application of electroencephalography (EEG), functional magnetic resonance, or positron emission tomography, even though it reports about findings analyzing other issues such as cardiac and hormonal responses, and the topic of doping in chess. In addition, the chapter addresses three central themes in the study of the brain of chess players: the activation of cerebral cortex areas, the hemispheric specialization, and the anatomical changes.