The development of the endocannabinoid (eCB) signaling system is closely intertwined with neurodevelopment, and evidence from both rodent and human studies suggests that the eCB system plays an important role in shaping responses to stress across neurobiological, physiological, and endocrine systems. Indeed, eCB signaling and genetic variation in endogenous eCB levels have been shown to influence the maturation of neuronal populations, sculpt structural and functional connectivity in youth and adults, and influence risk for anxiety and other stress-related disorders. In this chapter, we review how the eCB system interacts with ongoing postnatal neurodevelopment, citing examples from both rodent and human literatures, to potentiate risk and resilience to stress-related disorders.