Age-related macular degeneration (AMD) is a neurodegenerative disease and a leading cause of irreversible vision loss in the developed world. While not classically described as an inflammatory disease, a growing body of evidence has implicated several components of the innate immune system in the pathophysiology of age-related macular degeneration. In particular, complement activation, microglial involvement, and blood-retinal-barrier disruption have been shown to play key roles in disease progression, and subsequent vision loss. This review discusses the role of the innate immune system in age-related macular degeneration as well as recent developments in single-cell transcriptomics that help advance the understanding and treatment of age-related macular degeneration. We also explore the several potential therapeutic targets for age-related macular degeneration in the context of innate immune activation.