It is well established that stress has a major impact on memory, driven by the concerted action of various stress mediators on the brain. Recent years, however, have seen considerable advances in our understanding of the cellular, neural network, and cognitive mechanisms through which stress alters memory. These novel insights highlight the intricate interplay of multiple stress mediators, including-beyond corticosteroids, catecholamines, and peptides-for instance, endocannabinoids, which results in time-dependent shifts in large-scale neural networks. Such stress-induced network shifts enable highly specific memories of the stressful experience in the long run at the cost of transient impairments in mnemonic flexibility during and shortly after a stressful event. Based on these recent discoveries, we provide a new integrative framework that links the cellular, systems, and cognitive mechanisms underlying acute stress effects on memory processes and points to potential targets for treating aberrant memory in stress-related mental disorders.