Leukemia inhibitory factor (LIF) is a multi-function cytokine that has various effects on different tissues and cell types in rodents and humans; however, its insufficiency has a relatively mild impact. This could explain why only some aspects of LIF activity are in the time-light, whereas other aspects are not well known. In this review, the LIF structure, signaling pathway, and primary roles in the development and function of an organism are reviewed, and the effects of LIF on stem cell growth and differentiation, which are important for its use in cell culturing, are described. The focus is on the roles of LIF in central nervous system development and on the modulation of its physiological functions as well as the involvement of LIF in the pathogenesis of brain diseases and injuries. Finally, LIF and its signaling pathway are discussed as potential targets of therapeutic interventions to influence both negative phenomena and regenerative processes following brain injury.