The performance of most tasks with one hand, typically the right, is a uniquely human characteristic. Not only do people prefer to use one hand rather than the other, but also they usually perform tasks faster and more accurately with this hand. The study of manual asymmetries and what such performance differences between the two hands reveal about brain organization and motor function has been a topic of considerable research over the last several decades. The aim of this Research Topic is to review and further explore the origins of manual asymmetries and their relationship to handedness, unimanual and bimanual motor performance, and brain function. The articles included here involve original research conducted in humans or non-human models species, as well as theoretical perspectives, review articles, and meta-analyses.