•Studies of fear learning and extinction have advanced our understanding of the neurobiology of threat and safety learning.•Identifying and addressing knowledge gaps across animal and human studies is crucial for better cross-species translation.•Altered fear learning and extinction have been implicated in many brain disorders beyond post-traumatic stress disorder.•Our understanding of fear circuits can further enhance clinical benefits for a wide array of brain disorders. Over the past decades, studies of fear learning and extinction have advanced our understanding of the neurobiology of threat and safety learning. Animal studies can provide mechanistic/causal insights into human brain regions and their functional connectivity involved in fear learning and extinction. Findings in humans, conversely, may further enrich our understanding of neural circuits in animals by providing macroscopic insights at the level of brain-wide networks. Nevertheless, there is still much room for improvement in translation between basic and clinical research on fear learning and extinction. Through the lens of neural circuits, in this article, we aim to review the current knowledge of fear learning and extinction in both animals and humans, and to propose strategies to fill in the current knowledge gap for the purpose of enhancing clinical benefits.