Exogenous cannabinoids disrupt behavioral learning and impede induction of long-term potentiation (LTP) in the hippocampus, yet endogenous cannabinoids (endocannabinoids) transiently suppress inhibitory post-synaptic currents (IPSCs) by activating cannabinoid CB1 receptors on GABAergic interneurons. We found that release of endocannabinoids by a rat CA1 pyramidal cell during this depolarization-induced suppression of inhibition (DSI) enabled a normally ineffective train of excitatory post-synaptic currents (EPSCs) to induce LTP in that cell, but not in neighboring cells. By showing that endocannabinoids facilitate LTP induction and help target LTP to single cells, these data shed new light on the physiological roles of endocannabinoids and may lead to a greater understanding of their effects on behavior and potential clinical use.