The ventrolateral periaqueductal gray matter (vlPAG) is located in the ventrolateral region of the periaqueductal gray matter (PAG) of the midbrain, which includes γ‑aminobutyric acidergic neurons, glutamatergic neurons, and dopaminergic neurons. It contains neurochemicals such as 5‑hydroxytryptamine (5‑HT), glutamate, γ‑aminobutyric acid, and acetylcholine. The vlPAG has nerve fiber connections to many areas of the brain and is an important brain region involved in pain regulation. This article reviews the structural characteristics of vlPAG, the neurophysiological mechanism of vlPAG involved in pain regulation, and its connection with nerve fibers in other brain regions, and summarizes its key role in pain regulation, so as to provide basis and ideas for the development of more related analgesic drugs and methods.