Abstract: Alzheimer’s disease (AD) is an irreversible disease that leads to neurodegeneration. The underpinning mechanisms of neuronal cell death are a matter of ongoing debate regarding the impact of accumulation of the amyloid beta (Aβ) peptide and post-translation modifications of the tau protein. However, a growing area of research and one that may provide a more rigorous account of the early changes seen in Alzheimer’s brains is inflammation. Brain inflammation is a coordinated immune response to subtle changes in the brain’s microenvironment indicative of injury and disease. Neuroinflammation can be either short lived or chronic and lead to changes in brain structure and its neurochemistry. In AD, the ability of the brain to self-regulate inflammatory signals is compromised and leads to a chronic and deleterious inflammatory response. Understanding the molecular entities that are involved in neuroinflammation in AD will open the door to much needed novel therapeutic strategies. However, this is a cautionary tale with respect to the timing and exact nature of the proposed therapeutic strategy. In this perspective article, we will briefly introduce the current view of the dual nature of Toll-like receptor (TLR) 2 and TLR4-driven inflammation in AD and highlight why we believe that modulating the inflammatory status within a defined time window might provide a better therapeutic concept than globally supressing it for a prolonged time.