Neuroscience has made enormous progress during the past half century as new tools and technological advances have made it possible to ask increasingly specific questions about the structure and function of neurons, synapses, proteins, and genes. Progress has been slower in understanding the organization and function of circuits, networks, and brain systems. And in that context, it is sometimes overlooked how important it is to have an account of cognition itself ? perception, attention, memory, language, and the organization of action. One wants to understand its components and to understand how the components of cognition can be related to brain substrates. The work proposed herein addresses a fundamental issue about how the brain has organized its memory functions. The issue is whether short-term and long-term memory are indeed distinct entities, such that short-term memory is independent of the hippocampus (and related structures); or whether an exception to that principle exists in the case of spatial cognition. It is a deep and fundamental matter. Do the hippocampus and related structures have online, computational functions? Or are these structures in fact needed only when short-term memory capacity has been exceeded. To evaluate these two perspectives, five studies are proposed in individuals with hippocampal lesions (or larger lesions that include related structures) using navigation in open space, virtual reality, as well as a test of spatial imagining. Parallel work on path integration is proposed for rats with selective lesions of the hippocampal, entorhinal, or parietal cortex. Understanding the relationship between memory and spatial cognition is fundamental to understanding how the brain has organized its memory functions.