This study provides insight into seniors' perceptions of and responses to direct-to-consumer prescription drug advertising (DTCA) usefulness, examines support for DTCA regulation as a type of uncertainty management, and extends and gives empirical voice to previous survey results through methodological triangulation. In-depth interview findings revealed that, for most informants, DTCA usefulness was uncertain and this uncertainty stemmed from 4 sources. The majority had negative responses to DTCA uncertainty and relied on 2 uncertainty-management strategies: information seeking from physicians, and inferences of and support for some government regulation of DTCA. Overall, the findings demonstrate the viability of uncertainty management theory (Brashers, 2001, 2007) for mass-mediated health communication, specifically DTCA. The article concludes with practical implications and research recommendations.