This chapter offers a critical examination of John’s third medical work, On Psychic Pneuma. The first section deals with John’s audience, contextualizing his relationship with his dedicatee, Joseph Rhakendytes. John describes the psychic pneuma as the vehicle and first instrument of the soul; consequently, the purified state of this pneuma, achieved through an appropriate regimen, is essential to keeping Joseph’s bodily and spiritual health in good condition. It is then shown that, unlike earlier Greek and Byzantine theories on human physiology in which authors identified three kinds of pneumata, John identified four distinct pneumata: in the stomach, liver, heart, and brain, respectively. Furthermore, John introduced an innovative theory in which each of the four pneumata is correlated with two primary qualities (unnamed, ‘gastric’ pneuma: cold and moist; natural pneuma: warm and moist; vital pneuma: warm and dry; psychic pneuma: cold and dry). A close reading of John’s text unveils the major importance that is given throughout the treatise to the psychic pneuma, which is dispersed throughout the body via the nerves and is responsible for sensory and motor activities. Any disturbance in the quality, for example, of the psychic pneuma may affect its flow and can thus be a cause of impairment. Finally, it is pointed out that John made a direct connection between the quality of pneuma and one’s daily regimen, including diet, physical exercise, bathing, and sleep, thus providing a systematic introduction to the qualitative change in pneuma as an object of treatment.