Alzheimer’s disease is a progressive neurodegenerative disorder. It is the primary cause of dementia in the elderly and has no known cure. Recently, however, there has been an increased emphasis placed on the role of the human microbiome, the primarily bacterial residents of the human body, on the pathophysiology of Alzheimer’s. It is thought that the organisms that comprise the microbiome may be important drivers in shaping and controlling the physiology of various systems, including the central nervous system (CNS). Microbiota colonize the gut immediately during the postnatal period, and they play critical and lifelong roles in the development and functioning of the immune and metabolic system in the gut, as well as the brain. In this chapter, we will review the roles microbiota play in the pathophysiology of Alzheimer’s, with a focus on the microbiome–host and the gut–brain relationship. Specifically, we will introduce the molecular pathology and risk factors of Alzheimer’s, then focus on the microbial involvement and potential mechanisms underlying the disease, mechanisms which are largely linked to the pathological events and risk factors of Alzheimer’s. We will also discuss the opportunities for modulating microbiota as a strategy to develop useful therapeutics for Alzheimer’s. Collectively, an investigation of microbial involvement in Alzheimer’s will broaden our understanding of the pathogenesis of the disease and will highlight new potential avenues for developing microbiome-based therapeutics.