Despite the widespread presence of clinical anesthesiology in medical practice, the mechanism by which diverse inhalational agents result in the state of general anesthesia remains unknown. Over recent decades, our understanding of general anesthetic mechanisms has evolved dramatically from early unitary hypotheses, largely due to the development and influence of a myriad of scientific disciplines ranging from molecular biology to cognitive neuroscience. These discoveries have led to a renaissance of investigation into the mechanisms of general anesthetics and have generated both novel answers and questions. In this chapter, we review the major hypotheses of general anesthetic mechanisms of action and present an expanded overview of current investigation into those mechanisms. We also present a framework to aid in thinking about the actions of these agents, highlighting the relationship between putative targets at the molecular level and the more integrated functional changes in behavior and consciousness.