Memories that are emotionally arousing generally promote the survival of species; however, the systems that modulate emotional learning can go awry, resulting in pathological conditions such as post-traumatic stress disorders, phobias, and addiction. Understanding the conditions under which emotional memories can be targeted is a major research focus as the potential to translate these methods into clinical populations carries important implications. It has been demonstrated that both fear and drug-related memories can be destabilised at their retrieval and require reconsolidation to be maintained. Therefore, memory reconsolidation offers a potential target period during which the aberrant memories underlying psychiatric disorders can be disrupted. Monfils et al. (Science 324:951-955, 2009) have shown for the first time that safe information provided through an extinction session after retrieval (during the reconsolidation window) may update the original memory trace and prevent the return of fear in rats. In recent years, several authors have then tested the effect of post-retrieval extinction on reconsolidation of either fear or drug-related memories in both laboratory animals and humans. In this article, we review the literature on post-reactivation extinction, discuss the differences across studies on the methodological ground, and review the potential boundary conditions that may explain existing discrepancies and limit the potential application of post-reactivation extinction approaches.