When humans perform tasks involving spatial cognition and visual spatial thinking, like navigation, vehicle control, manual manipulation, or understanding of the structure of data, they must often deal with displays and controls of the work environment that are represented in different frames of reference. Such thinking is challenged by the need to perform transformations between these different reference frames. The frame of reference can be defined by three axes of translation and three axes of orientation, each with either static or dynamic properties. In this chapter we describe important human performance limitations that constrain visual–spatial thinking, as these are related to mental rotation and transformations of location. We describe how these limits have important implications for the design of different displays that support the user of three-dimensional spatial information, and support the user’s understanding of three-dimensional motion. Finally, we describe the implications of visual spatial thinking to two particular applications: helmet-mounted displays and information visualization.