Age-related macular degeneration (AMD), a complex disease stemming from both genetic abnormalities and environmental insults, is the most common form of visual impairment in elderly individuals of the Western world. Many potential etiologies are linked to AMD, but smoking is the leading environmental insult associated with this maculopathy. Smoke-induced damage is mediated in part through direct oxidation, depletion of antioxidants, complement activation, and vascular transmutations. Clinically, these mechanisms manifest themselves as keystones of atrophic AMD: retinal pigment epithelium degeneration, formation of extracellular deposits such as drusen, and thickening of Bruch's membrane. Furthermore, smoking induces angiogenesis and choroidal neovascularization, advancing the course of the disease to late-stage AMD. Further exploration of the biological processes affected by cigarette smoke exposure will provide greater insight into the pathogenesis of AMD.