Evidence accumulated over the past 20 y indicates that the anterior pituitary hormone, prolactin (PRL), is a critical, physiologically relevant immunomodulator. Results from early hormone-ablation studies in animals implicated PRL as a factor that contributes to maintenance of immunocompetence. However, the discovery of PRL receptors on T and B lymphocytes and the observation that these cells synthesize and secrete PRL spurred intensive investigation into the actions and underlying mechanisms triggered by the hormone in the immune system. In numerous cell culture systems, PRL was found to act as a co-mitogen, enhancing the efficacy of plant lectins and cytokines in the stimulation of lymphocyte proliferation. In addition, results from more recent studies suggest that PRL may promote survival of certain lymphocyte subsets presumably due to its capacity to augment expression of anti-apoptotic genes. In this review, we focus on the proliferative actions of PRL and its survival promoting properties in immune cells.