This article examines the neurobiological basis of the healing power attributed to shamanic practices in the Andes and Brazil in light of the pharmacology of neurotransmitters and the new technological explorations of brain functioning. The psychotropic plants used in shamanic psychiatric cures interfere selectively with the intrinsic neuromediators of the brain. Mainly they may alter: (1) the neuroendocrine functioning through the adrenergic system by controlling stressful conditions, (2) the dopaminergic system in incentive learning and emotions incorporation, (3) the serotoninergic system in modulating behaviors, and mood, and (4) basic functions implied in anxiety or depression. PET scans and functional magnetic resonance imaging studies of hypnotic trance and altered states of consciousness may provide a useful model for the neurophysiological phenomena of shamanic drum-and-dance trance. The reorganization of cortical areas and the direct interconnections between the prefrontal cortex and the dopaminergic reward centers in the limbic system are of particular significance for human social judgment and symbolic processing. Those centers—including the hypothalamus and the amygdala (associated with psychosomatic equilibrium, memory, and emotion) are enhanced. This arousal may be amplified in order to induce a cathartic crisis—the shamanic trance. It is suggested that through this holistic approach the shaman empirically interferes in neurobiological dysfunctions.