The 5-HT [subscript 3] receptor, the only ionotropic 5-HT receptor, is expressed in limbic regions, including the hippocampus, amygdala, and cortex. However, it is not known whether it has a role in fear memory processes. Analysis of 5-HT [subscript 3A] receptor knockout mice in fear conditioning paradigms revealed that the 5-HT [subscript 3A] receptor is not required for the acquisition or retention of fear memory but is essential for the extinction of contextual and tone-cued fear. Our data suggest that the 5-HT [subscript 3A] receptor could be a key molecule regulating fear memory processes and a potential therapeutic target for fear disorders.