The periaqueductal gray (PAG) is a mesencephalic brain structure involved in the integration and execution of active and passive self-protective behaviors against imminent threats. The PAG sends and receives projections to and from nuclei linked to drug addiction including the: (1) ventral tegmental area, (2) extended amygdala, (3) medial prefrontal cortex, (4) pontine nucleus, (5) bed nucleus of the stria terminalis, and (6) hypothalamus. Marichal-Cancino and VázquezLeon et al. discuss the key role of the PAG in drug addiction phenomena. In the cover image, a young person with marijuana craving seems confused while experiencing autonomic disturbances, desire for substances intake, and emotional alterations due to the complex neuronal circuits in which the PAG is importantly involved. See pages 1493–1509. (Cover art by Andrea Loza Hurtado and Jaime Hendrik Esparza Badillo).