The value of collaborative international research in addressing global public health challenges is increasingly recognized. However, little has been written about lessons learned regarding fieldwork to help guide future collaborative efforts. Through a research partnership between two Northern universities, one Southern university, and a Southern faith-based organization, we evaluated a school-based HIV prevention intervention with South African adolescents. In this article, we highlight the seven key fieldwork-related challenges experienced and identify the lessons learned. The underlying theme is that of reconciling a structured and reasoned "desk" planning process with the more fluid and unpredictable reality of conducting fieldwork. This concern is particularly significant in resource-deprived environments and/or contexts that are less familiar to Northern partners. Fieldwork is unpredictable, but obstacles can be minimized through meaningful participation in both planning and field research. Sharing practical lessons from the field can prove a useful resource for both researchers and practitioners.