Research on computer-supported instructional communication (CSIC) involves the study of interactions between instructors, learners, and system components in computer-based learning environments. At least two strands of research can be identified that are crucial for the understanding of CSIC: From the learning perspective, rooted in cognitive and educational psychology, CSIC is analyzed with regard to its potential for promoting specific cognitive processes, and thus ultimately for improving learning. From the communication perspective, rooted in social psychology and communication science, CSIC is analyzed with regard to conditions that affect its effectiveness and efficiency. CSIC researchers face the challenge of integrating the two traditionally separate research strands and their distinct methodological frameworks. In turn, new methods and findings emerging from an integrative application of research methods are leading to new conceptual challenges regarding the causal mechanisms mediating between the interindividual and the intraindividual levels in CSIC. We provide examples of CSIC research that demonstrate successful methodological integration, and introduce open conceptual challenges.