In this chapter, we summarize the current state of research that relates the inability to mentally operate with numbers to the development of brain mechanisms. Before looking at the details about longitudinal development of the neurocognitive underpinnings in numerical disorders we would like to briefly address the neural bases of typical numerical cognition and developmental dyscalculia. Here, we refer to the clinical classification of developmental dyscalculia, which defines it as a specific learning impairment affecting numerical cognition that emerges at a very early stage of development and cannot be explained by inappropriate schooling or lack of learning opportunities. Therefore, when we talk about developmental dyscalculia, we do not include acquired numerical disorders due to loss of an established ability (e.g. after brain damage). Rather, we focus on the inability to acquire numerical concepts or procedures due to developmental issues. Based on the knowledge generated in cross-sectional studies investigating numerical cognition, we elaborate on developmental changes in brain function and structure during typical development and in developmental dyscalculia. Finally, we discuss the predictive relation between brain characteristics and numerical skills.