Through multi-modal investigation of medial temporal lobe (MTL) function using high-resolution structural and functional magnetic resonance imaging (MRI), electrophysiological recordings, and imaging genetics, this dissertation investigates various remaining questions on the role of the hippocampal subregions during episodic learning and memory. Learning and recalling information from personal experiences (episodic) is central for everyday living; damage to the MTL results in an inability to learn new episodic information. This dissertation presents data from four experiments investigating the role of medial temporal structures during the learning and recall of episodic information. Using high-resolution functional MRI, we show that blood-oxygenated-level-dependent (BOLD) activity increases within the CA3 and dentate gyrus regions during encoding of novel associated contextual information of an episode and increases within the subiculum during retrieval of this learned information. Hippocampal CA1 activity increases and correlates to performance during learning of allocentric (viewpoint-independent) spatial information. Single neurons within the CA3 and dentate gyms differentiate in firing rate to similar episodes stored in memory. Additionally, these regions show BOLD decreases during episodic learning in older individuals who are genetically at-risk for Alzheimer's Disease. Overall, this dissertation supports the idea that separate hippocampal subregions contribute differently during the learning and recall of episodic information.