One of the most fundamental challenges to understanding episodic memories is to understand how we form, store, and retrieve memories of countless, interrelated memories. From an organizational perspective, this is a daunting task. It has been argued that forgetting may be a natural consequence of our normal mnemonic activities, or even an adaptive mechanism that allows memory systems to function efficiently. The present work is focused on three main themes related to the balance between remembering and forgetting of episodic memories. First, the consequences of repeated retrieval are considered, with a focus on the changes that take place both at the level of individual memories and at the level of the neural systems that guide competitive retrieval. Data is presented that argues for a direct relationship between demands placed on mechanisms in prefrontal cortex and forgetting of memories that prove to be irrelevant. These findings are considered in terms of an adaptive memory system, wherein interference between memories is detected and resolved by mechanisms in prefrontal cortex, with the gradual weakening of interfering memories lessening the demands on these prefrontal mechanisms. The second theme considered in this dissertation relates to the mechanisms that allow for previously irrelevant memories to be selectively retrieved in the face of interference from more dominant, but irrelevant memories. Such acts of retrieval are often required when retrieval goals change, with the ability to flexibly guide retrieval of obvious importance. Evidence is presented indicating that the same prefrontal mechanisms that benefit from the weakening of interfering memories are selectively recruited when these weakened memories must be retrieved. These data are considered with respect to other prefrontal mechanisms that support retrieval amidst competition. iii Finally, the third theme of this dissertation relates to the mechanisms that operate during encoding to help protect memories from interference-related forgetting. It is argued that while various neocortical and medial temporal lobe structures support successful encoding of episodic memories when no interference is present, engagement of these structures does not guard against interference-related forgetting. Rather, evidence is described highlighting the role of the hippocampus and surrounding cortex in supporting a mechanism that allows new learning to occur without profound forgetting of previously formed memories. Together, these studies highlight the cognitive and neural mechanisms that allow episodic memory to function in an adaptive manner, elucidating the factors that regulate the delicate balance between remembering and forgetting.