Müller glia, the main glial cell of the retina, are critical for neuronal and vascular homeostasis in the retina. During age-related macular degeneration (AMD) pathogenesis, Müller glial activation, remodeling, and migrations are reported in the areas of retinal pigment epithelial (RPE) degeneration, photoreceptor loss, and choroidal neovascularization (CNV) lesions. Despite this evidence indicating glial activation localized to the regions of AMD pathogenesis, it is unclear whether these glial responses contribute to AMD pathology or occur merely as a bystander effect. In this review, we summarize how Müller glia are affected in AMD retinas and share a prospect on how Müller glial stress might directly contribute to the pathogenesis of AMD. The goal of this review is to highlight the need for future studies investigating the Müller cell's role in AMD. This may lead to a better understanding of AMD pathology, including the conversion from dry to wet AMD, which has no effective therapy currently and may shed light on drug intolerance and resistance to current treatments.