Graphene is a two-dimensional material with unique properties, such as superb mechanical strength and carrier mobility. Similarly to semiconductors, however, graphene is not very useful for applications in its pristine form; rather, it must be “functionalized” through judicious manipulation of defects, impurities, and adsorbates. In this article, we provide an overview of the intrinsic defects in graphene, such as vacancies, interstitials, and line defects, and their potential role in transport and other properties. We also discuss impurities and adsorbates that can act as dopants to enhance carrier densities, controlling n- and p-type conduction for transistor applications, and can serve as reactive sites for catalytic and sensor applications. Although functionalization holds significant promise, realization of that potential remains an open pursuit.