Fear is an emotion that is central to the organization of defensive behaviors in response to threat, and therefore has an essential role in survival for animals. Unfortunately, in some cases, dysfunction in the fear system produces inappropriate and exaggerated fears that lead to psychiatric disorders, such as post-traumatic stress-disorder (PTSD). These disorders severely affect the lives of patients and are an increasing burden on our societies. Therefore, understanding the molecular mechanisms underlying fear memory processes could help with the development of therapeutic strategies for fear disorders. The 5-HT3 receptor is the only ionotropic receptor in the family of 5-HT receptors. In the brain, the 5-HT3A receptor is mainly expressed in limbic regions, such as hippocampus, amygdala and cortex, suggesting its involvement in cognitive and emotional brain functions. However, it is not known whether the 5-HT3 receptor regulates fear memory processes. Analysis of 5-HT3A receptor knockout mice in fear conditioning paradigms revealed that the 5-HT3A 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-HT3A receptor could be a key molecule regulating fear memory processes and a potential therapeutic target for fear disorders.