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Abstract The study of Alzheimer's disease (AD) has led to an increased understanding of the multiple pathologies and pathways of the disease. As such, it has been proposed that AD and its various stages might be most effectively treated with a combination approach rather than a single therapy; however, combination approaches present many challenges that include limitations of non‐clinical models, complexity of clinical trial design, and unclear regulatory requirements. The Alzheimer's Association Research Roundtable meeting on May 7–8, 2018, discussed the approaches and challenges of combination therapy for AD. Experts in the field (academia, industry, and government) provided perspectives that may help establish a path forward for the development of new combination therapies.