<p>Post-traumatic stress disorder (PTSD) persists when stress biases memory systems—broadening threat engrams, weakening context-appropriate inhibition, and rendering extinction fragile. Integrating preclinical and human evidence, we argue that these liabilities are tractable within a circuit-informed framework that aligns behavioral procedures with the biology of fear memory. Extinction can be stabilized by preferentially engaging hippocampal–prefrontal–amygdala pathways and their thalamic coordinators; targeted training and sleep-based reactivation strengthen top-down control over intrusions and sharpen discrimination between safety and threat. Brief, prediction-error–rich retrieval opens a reconsolidation window through which maladaptive content can be updated; pairing this window with state-aligned neuromodulation or phase-specific psychedelic pharmacology biases plasticity toward safety without relying on nonspecific anxiolysis. Framed this way, integrating extinction reinforcement with voluntary memory control and reconsolidation editing offers a coherent route to more durable relief from traumatic memories in PTSD.</p>