While many factors have been studied in blended learning, the influence of a given discipline on design considerations and possibilities is rarely illuminated. However, different disciplinary goals and objectives, curricular demands and constraints, and other discipline-specific features significantly influence the variety of blended learning designs. In this chapter, three examples of blended learning design are described to highlight the role of disciplinary differences in shaping blended opportunities. One example focuses on the design of a graduate program in educational leadership, the second discusses the design of a cross-national course on humanities for technology majors, and the third focuses on the design of an undergraduate engineering program. By considering these three cases, both independently and comparatively, the influence of a discipline in the blended learning design and decision-making process, alongside other instructional and strategic considerations are established. These cases also highlight how the open-endedness of what “blended” means is an asset, not a detriment, to blended learning because it affords a range of creative design possibilities that best fit learners’ needs and disciplines. The chapter concludes with a discussion on blended design variations informed by different disciplinary needs and requirements to prompt the generation of additional creative options that may fit varying learning needs.