The ability to find one's way in our complex environments represents one of the most fundamental cognitive functions. Although involving basic perceptual and memory related processes, spatial navigation is particularly complex because it is a multisensory process in which information needs to be integrated and manipulated over time and space. Not surprisingly, humans differ widely in this ability, and recent animal and human work has begun to unveil the underlying mechanisms. Here, we consider three interdependent domains that have been related to navigational abilities: cognitive and perceptual factors, neural information processing and variability in brain microstructure. Together, the findings converge into an emerging model of how different factors interact to produce individual patterns of navigational performance.