The e-learning 2.0 transformation of continuing education of healthcare professionals (CE/CME) will be characterized by a fundamental shift from the delivery of static information online to a seamless, digital operation in which all users have the ability to access, create, and share knowledge in a multidimensional, instantaneous, collaborative, and interactive manner. This transformation will be disruptive, blurring existing boundaries between CE/CME professionals, content experts, and student learners, and modifying the traditional structured learning process to a more informal one. While the opportunities are unlimited, the transformation will present not only technology challenges but also social and educational challenges. Recent experiences with similar disruptive technologies show that a meaningful transformation can be achieved only if the application of technology is accompanied by strategic operational changes. This chapter offers a conceptual framework to guide CE/CME professionals interested in transforming their operations with new e-learning 2.0 technologies. Employing several usage scenarios, a new e-learning 2.0-based model of CE/CME operation is introduced. We also present several examples of approaches adopted by our academic group to address the various challenges discussed in this chapter.