Discussion of human use and conceptualization of space is incomplete without understanding the spatial abilities of a large group of people whose primary medium of communication is visuo-spatial—users of sign language. Multiple studies indicate that users of sign language are better than non-signers at processing and manipulating spatial information (Colmenero et al. 2004; Springford 2006), owing to experience with the inherently present spatial component in signed languages. In this chapter, we provide a summary of what is currently known about space use, processing, and conceptualization by signers. In the first section, we explain how the use of space pervasively defines the linguistic system of sign languages at every scale of analysis, from formational parameters to discourse level. In the second section, we demonstrate how information processing based on the use of space affects perceptual, memory, and language networks. In the third section, we explore implications of sign-language learning for enhancement of visual perception, memory, and space representation in non-native1 signers. considers visualization, both external (for example, diagrams and maps) and internal (imagery and other mental spatial representations); embodied cognition and spatial understanding; and the development of specific spatial curricula and literacies.