In recent years, private foundations have gained considerable relevance in global health due to their increasing presence in both financing and policy-making. Despite this, the question of how these actors make decisions on their funding priorities is under researched. The aim of this study is to understand and assess the relative importance of different factors in foundations’ decision-making. This question is important not only for actors in the global health arena, but for foundations that are under increasing pressure to be legitimate, effective and accountable players. This is a qualitative research study on the decision-making of foundations investing in global health. It applies a multiple case study methodology in the study of three foundations: the Bill & Melinda Gates Foundation, the Rockefeller Foundation and the Wellcome Trust. In-depth interviews with forty-six informants represented the main method for data collection. A qualitative thematic content analysis has been applied to both documentary sources and interviewees’ accounts. A strategic management approach has been used to de-construct the decision-making process into strategic planning and grant-making. As a first area of inquiry, this study sought to understand how foundations’ origins, governance structure and funding ethos are relevant in influencing their decision-making behavior. Second, this study sought to assess the relative importance of different factors (e.g., private partnerships or foundations’ networks) in influencing foundations’ decisions. Findings suggest influence is an overt objective of foundations' strategies. Leaders and networks are extremely important in both strategic planning and grant-making. By discussing findings through the perspective of major strategic management schools of thought, the study provides an in-depth understanding of foundations’ strategic planning and grant-making processes and recommendations to increase accountability, legitimacy and effectiveness. The analysis also introduces a re-conceptualization of foundations’ decision-making, and offers implications on the role of philanthropy in global health.