The immune system protects the host against noxious insults, to maintain homeostasis and restore functionality. The retina is known as an immune privileged tissue due to its unique anatomic and physiologic properties. The retina has its own defence system including resident immune cells and the complement system. Retinal degenerative diseases are a major cause of blindness worldwide; the aetiology of each differs and inflammation plays a pivotal role in the development of these diseases. For example, inherited retinal degenerations are caused by specific gene mutations, an inflammatory response is secondary to photoreceptor death and may further participate in disease progression. Dysregulation or malfunction of the parainflammatory response contributes to age-related macular degeneration. Diabetic retinopathy is a major microvascular complication of long-term diabetes, which has a significant impact on the immune system. Glaucoma is a heterogeneous disorder related to retinal ganglion cell death from increased intraocular pressure. Neurodegenerative insults and glial activation initiate an immune response to restore tissue homeostasis and facilitate tissue repair and remodelling. This chapter discusses the basic principles of the immune response to common retinal insults in pathophysiological conditions and the contribution of such responses to retinal degeneration.