Delirium is the most common complication found in the general hospital setting. Yet, we know relatively little about its actual pathophysiology. This article contains a summary of what we know to date and how different proposed intrinsic and external factors may work together or by themselves to elicit the cascade of neurochemical events that leads to the development delirium. Given how devastating delirium can be, it is imperative that we better understand the causes and underlying pathophysiology. Elaborating a pathoetiology-based cohesive model to better grasp the basic mechanisms that mediate this syndrome will serve clinicians well in aspiring to find ways to correct these cascades, instituting rational treatment modalities, and developing effective preventive techniques.