Navigation is a central part of daily life. For some, getting around is easy, while others struggle. Some clinical populations, such as those with Alzheimer’s Disease, display wandering behaviors and extensive disorientation. Working at the interface between immersive virtual reality and neuroimaging techniques, my research uses these complementary approaches to inform questions about how we acquire and use spatial knowledge. In this talk, I will discuss both some of my recent work and current experiments that center on three main themes: 1) how we learn new environments, 2) how the brain tracks spatial information, and 3) how individuals differ in their spatial abilities. My work also examines changes in the brain across the lifespan, including major transitions such as menopause and pregnancy. More broadly, I will discuss how navigation lends insight into processes of human learning and memory. The behavioral and neuroimaging studies presented in this talk inform new frameworks for understanding spatial knowledge, leading to novel approaches to answering the next major questions in navigation, learning, and memory.