The study by Andero and colleagues reported in this issue (6) examines the effect of a recently discovered small-molecule agonist of TrkB receptors on emotional learning. The compound, 7,8-dihydroxyflavone (7,8-DHF), was identified in a chemical screen of small molecules as a selective TrkB receptor agonist in vitro (5). A subsequent study (7) showed that this compound, when administered systemically in rodents, is neuroprotective and rescues BDNF deficits in a mouse model with reduced BDNF expression. Andero et al. administered 7,8-DHF systemically to rodents and found activation of TrkB receptors in the amygdala and enhanced acquisition of conditioned fear. Moreover, administration of 7,8-DHF was shown to enhance extinction of conditioned fear, a BDNF-dependent process. Deficits in extinction of conditioned fear have been suggested to underlie aspects of fear-based pathophysiology, such as posttraumatic stress disorder (8, 9). Andero et al. go on to show that 7,8-DHF enhances extinction of conditioned fear in mice that had previously been stressed. The ability of 7,8-DHF to enhance extinction of conditioned fear in naive animals—and, more importantly, in stressed animals in which extinction deficits may underlie the response—is provocative and could have important implications for the treatment of fear and stress disorders.