Background: School-based alcohol and other drug use prevention remains an important national strategy. Collaborative partnerships between universities and high schools have the potential to enhance prevention programming; however, there are challenges to sustaining such partnerships. Purpose: The purpose of this commentary is to underscore challenges faced by health education practitioners when implementing and sustaining a university-high school partnership-based alcohol and other drug education program, emphasize strategies for addressing these challenges, and discuss implications for practice based on lessons learned. Three common themes emerged: (a) lack of regular face-to-face meetings, (b) novice implementation personnel, and (c) teacher turnover. Strategies for overcoming these challenges are presented in this commentary and discussed in detail. Translation to Health Education Practice: Program developers ought to consider lessons learned presented in this commentary to enhance and sustain university-high school partnerships in health promotion.