This article considers the application of selected components of self-regulated learning (SRL; Zimmerman 2000) to student-content interaction in online learning and distance education (DE). In particular we discuss how, when interacting with electronically enhanced text, students must carefully employ self-regulated learning strategies that include planning, goal setting, self-monitoring processes, and calibration judgments. Because the student is often learning independently in DE courses, and because of the potential for non-linear navigation through online learning materials, we argue that the careful deployment of SRL skills is especially critical for successful outcomes. Consequently we discuss examples of how the demands of student-content interactions put students with self-regulation difficulties at risk of failure. We highlight research on learners who have poor SRL skills, inadequate calibration capabilities, and low executive functions in order to highlight areas of particular difficulty and areas in which support might be most beneficial. We conclude with the recognition that while support strategies can be derived from the research literature, there is a great need for research that addresses questions about student-content interaction in DE course settings specifically, and pertains to the increasingly diverse group of learners who take these courses.