Neuroinflammation is an important aspect of many diseases of the eye, and experimental animal models have been widely used to determine its impact on retinal homeostasis and neuron survival. Physical separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) results in activation and infiltration of macrophages. Numerous studies have shown the critical role of macrophages in retinal disease processes. In retinal detachment, accumulation of macrophages in the subretinal space is associated with changes in cytokine and chemokine profile which lead to photoreceptor cell death. Targeted disruption of macrophage chemotaxis significantly reduces retinal detachment-induced photoreceptor degeneration. Apoptosis is the predominant mechanism of cell death; however regulated necrosis is also a contributor of photoreceptor loss. Therefore, effective neuroprotective approaches could integrate combined inhibition of both apoptotic and regulated necrosis pathways.