Educational encounters of the future (and increasingly, of the present) will involve a complex collaboration of human and machine intelligences and agents, partnering to enhance learning and growth. Increasingly, "students and instructors are not only talking 'through' machines, but also [talking] 'to them', and 'within them'" (Edwards & Edwards, in press, p. 185). Instructional communication scholars have much to contribute to the theory and practice of human-machine communication (HMC). Important instructional concepts (e.g., immediacy, credibility, confirmation, motivation, learning) will be present in every interaction when one of the actors is replaced with a machine or when the interaction happens in a simulated world. Little is known however of how to promote effectiveness for both instructors and students in HMC. The authors believe artificial intelligence, social robotics, and virtual worlds are three areas instructional communication research should explore. They argue that while HMC is in its infancy, there is much to be gained by instructional communication researchers gearing up for this emerging line of research. As in the face-to-face classroom, the field would shed light on future possibilities and ways to foster better teaching and learning with machine agents and in machine worlds.