This article presents a review of the neural and neurochemical regulation of maternal behavior in the rat, emphasizing the role of the medial preoptic area (MPOA) and its neural connections in this regulation. Evidence for the role of the MPOA includes the following and will be discussed: (1) Axon-sparing lesions of the MPOA disrupt maternal behavior, indicating the involvement of MPOA neurons rather than fibers of passage. (2) Estradiol acts on the MPOA to facilitate maternal behavior. (3) An MPOA-to-lateral preoptic area-to-ventral tegmental area circuit may be part of the output pathway by which the MPOA influences maternal behavior. (4) MPOA neural circuitry may interact with olfactory neural circuitry and with the motor system to influence maternal responsiveness. (5) Opioid neural pathways appear to inhibit, and oxytocinergic neural pathways appear to promote, maternal behavior.