With the increased availability of computers and Internet technologies, computer-mediated learning environments are on the rise in both higher education and corporate sectors of society. At the same time there has been an increased awareness among educators and researchers of the importance of human interaction in the learning process. Computer-mediated groupwork is an instructional strategy that combines online technologies with human interaction. This chapter defines computer-mediated learning groups and outlines critical differences between learning groups and work groups. The chapter further explores benefits and challenges associated with using groupwork in online learning environments. Case examples and research related to (1) creating the groups, (2) structuring group activities, and (3) facilitating group interactions are provided.