Over the past century, psychologists have discussed whether forgetting might arise from active mechanisms that promote memory loss to achieve various functions, such as minimizing errors, facilitating learning, or regulating one's emotional state. The past decade has witnessed a great expansion in knowledge about the brain mechanisms underlying active forgetting in its varying forms. A core discovery concerns the role of the prefrontal cortex in exerting top-down control over mnemonic activity in the hippocampus and other brain structures, often via inhibitory control. New findings reveal that such processes not only induce forgetting of specific memories but also can suppress the operation of mnemonic processes more broadly, triggering windows of anterograde and retrograde amnesia in healthy people. Recent work extends active forgetting to nonhuman animals, presaging the development of a multilevel mechanistic account that spans the cognitive, systems, network, and even cellular levels. This work reveals how organisms adapt their memories to their cognitive and emotional goals and has implications for understanding vulnerability to psychiatric disorders.