Age-related macular degeneration (AMD) is one of the most well-characterized late-onset, complex trait diseases. Remarkable advances in our understanding of the genetic and biological foundations of this disease were derived from a recent convergence of scientific and clinical data. Importantly, the more recent identification of AMD-associated variations in a number of complement pathway genes has provided strong support for earlier, paradigm-shifting studies that suggested that aberrant function of the complement system plays a key role in disease etiology. Collectively, this wealth of information has provided an impetus for the development of powerful tools to accurately diagnose disease risk and progression and complement-based therapeutics that will ultimately delay or prevent AMD. Indeed, we are poised to witness a new era of a personalized approach toward the assessment, management, and treatment of this debilitating, chronic disease.