Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly individuals worldwide. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of AMD. This review discusses historical and more recent studies that have led to the recognition that AMD is an intraocular inflammatory disease, and that is possibly driven by an immune response. A particular focus of this review is recent studies on the contribution of the complement system and macrophages to the pathogenesis of AMD. A working hypothesis is also presented that may reconcile the current understanding of the pathogenesis of AMD and some apparently contradictory findings in the literature.