The production of emotional tears appears to be uniquely present in Homo sapiens. Despite the ubiquity of this human behavior, research is only just beginning to uncover the neurobiologic underpinnings of human emotional crying. In this article, we review the current state of the literature investigating the neurobiologic aspects of this uniquely human behavior, including the neuroanatomical, neurochemical, and psychophysiologic findings. To set the context for this review, we first provide a brief overview of the evolutionary background and functions of tearful crying. Despite an accumulating understanding of the neurobiology of human emotional crying, the primary sources of information are currently from animal studies and observations in neurologic patients suffering from pathologic crying. Currently, most of the research on the neurobiology of crying in humans has focused on autonomic physiologic processes underlying tearful crying, which may yield essential clues regarding the neural substrates of the production of crying behavior and its effects on the crier. Further challenges in elucidating the neurobiology of crying involve the complexity of crying behavior, which includes vocalizations, tear production, the involvement of facial musculature, subjective emotional experience, emotion regulatory behaviors, and social behaviors. Future research is needed to comprehensively characterize the neurobiology of this intriguing and complex human behavior.