Global diseases require collaboration at multiple scales – from local to global. This article examines the experience of three international global public health partnerships – UNAIDS, the Stop TB Partnership and the Roll Back Malaria Partnership. These partnerships must be understood as compound collaborations. Such collaboration can often exhibit a marked tension between loose and tight coupling. Strategically designed to be loose or flexible in order to build initial support, loose institutional arrangements can also render these partnerships ineffective. Focal institutions, however, can help to align and facilitate the contributions of different partners operating on different scales.