Modulation of respiration is a prerequisite for survival of the individual and of the species. For example, respiration has to be adjusted in case of speech, strenuous exercise, laughing, crying, or sudden escape from danger. Respiratory centers in pons and medulla generate the basic respiratory rhythm or eupnea, but they cannot modulate breathing in the context of emotional challenges, for which they need input from higher brain centers. In simple terms, the prefrontal cortex integrates visual, auditory, olfactory, and somatosensory information and informs subcortical structures such as amygdala, hypothalamus, and finally the midbrain periaqueductal gray (PAG) about the results. The PAG, in turn, generates the final motor output for basic survival, such as setting the level of all cells in the brain and spinal cord. Best known in this framework is determining the level of pain perception. The PAG also controls heart rate, blood pressure, micturition, sexual behavior, vocalization, and many other basic motor output systems. Within this context, the PAG also changes the eupneic respiratory rhythm into a breathing pattern necessary for basic survival. This review examines the latest developments regarding of how the PAG controls respiration.