Schemas are superordinate knowledge structures that reflect abstracted commonalities across multiple experiences, exerting powerful influences over how events are perceived, interpreted, and remembered. Activated schema templates modulate early perceptual processing, as they get populated with specific informational instances (schema instantiation). Instantiated schemas, in turn, can enhance or distort mnemonic processing from the outset (at encoding), impact offline memory transformation and accelerate neocortical integration. Recent studies demonstrate distinctive neurobiological processes underlying schema-related learning. Interactions between the ventromedial prefrontal cortex (vmPFC), hippocampus, angular gyrus (AG), and unimodal associative cortices support context-relevant schema instantiation and schema mnemonic effects. The vmPFC and hippocampus may compete (as suggested by some models) or synchronize (as suggested by others) to optimize schema-related learning depending on the specific operationalization of schema memory. This highlights the need for more precise definitions of memory schemas.