Prolactin (PRL) is mainly a pituitary neurohormone with pleiotropic actions and functions in the brain and other organs. PRL is a pleiotropic neurohormone acting on various tissues and organs, including the brain. PRL is secreted under a circadian rhythm mainly by the pituitary lactotroph cells but also by other tissues and organs. Its secretion is stimulated by several physical and psychological stress factors and influenced by various neurotransmitters. Initially named concerning its lactation role, it has pleiotropic effects. PRL mediates maternal and parental behaviors and attachment patterns; further, it neuromodulates neuroendocrine and behavioral stress responses with anxiolytic and antistress effects. Additionally, PRL acts as a cytokine, modulates the immune system, and it is involved in inflammation and autoimmunity, thereby potentially contributing to depression, which is comorbid to both mentioned phenomena.