The rapidly expanding range of options available for innovative e-learning approaches based on emerging technologies has given renewed importance to teaching and learning issues that have long been familiar to distance educators. These issues arise from the separation between learners, and between teacher and learners, which occurs when learning is undertaken wholly or partly online. There may be important implications that emerge from aspects of separation, depending on whether students are studying primarily on-campus, off-campus, trans-nationally, or in specific contexts such as the home, the workplace, fieldwork locations, or other places made possible by mobile learning technologies. We suggest that the context of learning has significant implications for e-learning design, and that one way of analysing these implications is to draw on understandings from distance education, particularly the theory of transactional distance. We use cases from two Australian universities to illustrate the practical application of these implications to e-learning design, including designs that involve Web 2.0 technologies.