The major functions of the midbrain periaqueductal gray (PAG), including pain and analgesia, fear and anxiety, vocalization, lordosis and cardiovascular control are considered in this review article. The PAG is an important site in ascending pain transmission. It receives afferents from nociceptive neurons in the spinal cord and sends projections to thalamic nuclei that process nociception. The PAG is also a major component of a descending pain inhibitory system. Activation of this system inhibits nociceptive neurons in the dorsal horn of the sinal cord. The dorsal PAG is a major site for processing of fear and anxiety. It interacts with the amygdala and its lesion alters fear and anxiety produced by stimulation of amygdala. Stimulation of PAG produces vocalization and its lesion produces mutism. The firing of many cells within the PAG correlates with vocalization. The PAG is a major site for lordosis and this role of PAG is mediated by a pathway connecting the medial preoptic with the PAG. The cardiovascular controlling network within the PAG are organized in columns. The dorsal column is involved in pressor and the ventrolateral column mediates depressor responses. The major intrinsic circuit within the PAG is a tonically-active GABAergic network and inhibition of this network is an important mechanism for activation of outputs of the PAG. The various functions of the PAG are interrelated and there is a significant interaction between different functional components of the PAG. Using the current information about the anatomy, physiology, and pharmacology of the PAG, a model is proposed to account for the interactions between these different functional components.