Objectives. The purpose of this research was to examine physicians' and patients' question-asking about medications during medical encounters. Methods. A dataset of 467 audiotapes and transcripts of outpatient visits, as well as postvisit interviews with chronic disease patients and their primary care physicians, was analyzed. Results. All patients took at least one prescribed medication and were using an average of 3.9 continued medications. Physicians and patients spent an average of 3.94 minutes, or 20% of each medical visit, discussing medications. Physicians asked patients an average of 9.3 questions about medications during each medical visit. Physicians asked significantly more questions of non-white patients, lower-income patients, and patients using more continued medications. Almost half (47%) of the patients observed did not ask any medication questions at all even though they were currently taking at least one medication; for those patients who did ask questions, the average number asked was 2.4. Starting a new medication doubled a patient's likelihood of question-asking. Physicians perceive question-asking in a positive light; patients who asked questions about medication were rated by their physicians as more interested and assertive than patients who did not ask questions, but not any more irritated or angry. Conclusions. The findings of the study illustrate the importance of improving physicians' and patients' question-asking about medications in primary care settings so that potential problems with medications can be detected and avoided and patient compliance can be improved.