Degeneration of cells in the retina is a hallmark of various inherited and acquired blinding diseases in humans. One of the most challenging problems to establish successful treatments for these diseases is to understand the molecular mechanisms that result in retinal degeneration and to identify endogenous rescue pathways which support cell survival. In many mouse models for retinal degeneration, expression of LIF in glial cells in response to a disease condition is crucial for the activation of an elaborate protective system. This mini review will summarize the findings that are related to LIF signaling and discuss the neuroprotective effects of LIF in different animal models.