Suicide is a complex problem linked to genetic, environmental, psychological and community factors. For the Aboriginal population more specifically, loss of culture, history of traumatic events, individual, family and community factors may also play a role in suicidal behaviour. Of particular concern is the high rate of suicide among Canadian Aboriginal youth. While the need to develop interventions to reduce suicidal behaviour for First Nations on-reserve populations is evident, there may be an element of distrust of researchers by Aboriginal communities. Furthermore, research in mental health and specifically suicide is much more sensitive than studying medical illnesses like diabetes. Clearly, this issue requires a unique and insightful approach. While numerous suicide prevention/intervention plans and guidelines have been published specifically for work involving Aboriginal people, the literature lacks a comprehensive discussion of the methodological and logistical issues faced by research teams and Aboriginal communities attempting to develop culturally-grounded and community-specific suicide prevention and intervention strategies. This paper outlines the research process, key challenges and lessons learned in a collaborative University-First Nations suicide prevention project conducted with eight north-western Manitoba First Nations communities (Canada).