This chapter aims to understand the concept of how and why general anesthetics (GA) should be considered as context-dependent modulators of neural plasticity, some definitions on plasticity. It presents the potential impact of the drugs on the developing central nervous system. The chapter discusses the mechanisms of plasticity in the context of anesthesia exposure in the adult brain. It explores the therapeutic role of general anesthesia in major depressive disorders and explains fundamental molecular and cellular mechanisms linking neural plasticity to these phenomena. Neural plasticity can be defined as changes in neuronal systems due to changed environment or altered homeostatic conditions. In addition to providing a potential framework for future neuroprotective approaches, results also bring important arguments in favor of the possibility that GA are powerful modulators of highly relevant signaling pathways implicated in the modulation of neural plasticity. In adults, GA has been shown to interfere with cellular and molecular events subserving the maintenance of plasticity.