The goal of this article is to explore the various ways that superintendents have responded to accountability-based educational reform efforts such as No Child Left Behind, the factors that have influenced their responses, and the implications of these responses for current and future educational leaders. With respect to the first issue, empirical data from a number of national studies (T. E. Glass & Franceschini, 2007; Johnson, Arumi, & Ott, 2006; Johnstone, Dikkers, & Luedeke, 2009; Stecher et al., 2008) make clear that while there have been a variety of responses from superintendents to accountability-based reform efforts, superintendents have mostly played a supportive role. Examining the situation more fully suggests that the driving factors behind superintendent support for accountability-based educational reform are complex and are often deeply embedded within the "DNA" of the role of superintendent. This article examines the structure of this DNA by looking at the factors that influence superintendents' views of accountability-based educational reform from historical, political, and institutional perspectives. This multifaceted approach provides new insights into the complex relationship that exists between the structure of the role of superintendent and the agency of the individuals who inhabit that role.