This paper explores culturally-related concerns that arose during a multi-year study of obsessive-compulsive disorder (OCD) along the U.S.-Mexico border and describes adaptations made to better connect the research process to study participants. The purpose of this exploration is two-fold: (1) to offer suggestions for culturally sensitive borderland mental health research; and (2) to enhance dialog focused on culture, mental health research and the U.S.-Mexico border. Systematic coding of the written record of weekly research team meetings identified six recurring cultural concerns: emotionally charged and poorly understood terminology; differing meanings of ethnicity and acculturation; quality of life-regional variation and uncertainty; overlap of research and care; hopeful but hesitant; and fatalism. We conclude that diligence in the initial planning phase of a study is only part of the challenge in doing culturally sensitive research. Equally important is an ongoing process of evaluation to make explicit cultural concerns that arise during research, as well as a readiness to implement culturally sensitive research adaptations.