The idea of differentiated instruction is an old one. The writings of Confucius note that learners differ in their gifts and talents and that to teach them well, the teacher must start where the individuals are. A century or more ago, one-room schoolhouses across the United States almost inevitably called on teachers to differentiate instruction in a single classroom that typically housed students between the ages of six and 16. Teachers in multi-age classrooms have, for decades, by intent and necessity practiced differentiation. More recently, models such as Universal Design for Learning and Response to Intervention (RtI) guide teachers in planning for and teaching with student differences in the forefront of their work. It is likely that most parents practice some sort of differentiation as they discover how remarkably different two or three or four children in the same family can be. All of these examples are rooted in the observations that, inconvenient as it might be, humans vary as learners, and that to help them develop as fully as possible, the adults in their lives need to know them and respond to them, at least to some meaningful degree, on the learners’ own terms. What this chapter will refer to as “differentiated instruction” is a more contemporary framework based on those same observations and rooted in research from multiple facets of education. This chapter will provide an overview of differentiation and the roles it might play in education of high-ability and high-potential learners.