When presented in a neutral context, emotional items interfere with episodic encoding of temporally contiguous non-emotional items, resulting in dissociable valence-dependent retrograde and arousal-dependent anterograde modulatory effects. By studying two rare patients with congenital lipoid proteinosis (Urbach-Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we demonstrate that this bidirectional modification of episodic encoding by emotion depends on the integrity of the amygdala, as both retrograde and anterograde modulatory effects are absent. Our findings implicate the amygdala in a neural circuitry that orchestrates rapid retrograde and anterograde regulation of episodic memory access upon criteria of behavioral significance.