A variety of neurotrophic factors can influence the cell functions of the developing, mature and injured retinal ganglion cells. The discovery that retinal ganglion cell loss can be alleviated by neurotrophic factors has generated a great deal of interest in the therapeutic potential of these molecules. Recently, evidence has provided valuable information on the receptors that mediate these events and the intracellular signaling cascades after the binding of these ligands. Signaling by neurotrophic factors does not seem to restrict to retrograde messenger from the target but also includes local interactions with neighbouring cells along the axonal pathways, anterograde signaling from the afferents and autocrine signaling. More insight into the mechanisms of action of neurotrophic factors and the signal transduction pathway leading to the protection and regeneration of retinal ganglion cells may allow the design of new therapeutic strategies.