Several usability issues were encountered during the design of a blended e-learning program for a course in evidence-based medicine for general practice trainers. The program was developed in four steps. We focused in this article on step 2 and 3. Step 2 focused on which educational principles to apply, that is, which learning theories, instructional designs and other theories should influence the program. Step 3 focused on the design elements, namely whether to use hypermedia and/or multimedia, and what screen design and which font to use. This article presents the important issues in designing an e-course and provides an impression of the complexity of designing high quality e-learning in particular for continuing medical education (CME).