Healthcare systems worldwide face a wide range of challenges, including demographic change, rising drug and medical technology costs, and persistent and widening health inequalities both within and between countries. Simultaneously, issues such as professional silos, static medical curricula, and perceptions of "information overload" have made it difficult for medical training and continued professional development (CPD) to adapt to the changing needs of healthcare professionals in increasingly patient-centered, collaborative, and/or remote delivery contexts. In response to these challenges, increasing numbers of medical education and CPD programs have adopted e-learning approaches, which have been shown to provide flexible, low-cost, user-centered, and easily updated learning. The effectiveness of e-learning varies from context to context, however, and has also been shown to make considerable demands on users' motivation and "digital literacy" and on providing institutions. Consequently, there is a need to evaluate the effectiveness of e-learning in healthcare as part of ongoing quality improvement efforts. This article outlines the key issues for developing successful models for analyzing e-health learning.