Mental rotation is a hypothesized imagery process that has inspired controversy regarding the substrate of human spatial reasoning. Two central questions about mental rotation remain: Does mental rotation depend on analog spatial representations, and does mental rotation depend on motor simulation? A review and meta-analysis of neuroimaging studies help answer these questions. Mental rotation is accompanied by increased activity in the intraparietal sulcus and adjacent regions. These areas contain spatially mapped representations, and activity in these areas is modulated by parametric manipulations of mental rotation tasks, supporting the view that mental rotation depends on analog representations. Mental rotation also is accompanied by activity in the medial superior precentral cortex, particularly under conditions that favor motor simulation, supporting the view that mental rotation depends on motor simulation in some situations. The relationship between mental rotation and motor simulation can be understood in terms of how these two processes update spatial reference frames.