This dissertation explores how people address problems of real human concern in situations of complexity, ambiguity, uniqueness, conflicting values and rapid change. Such circumstances stretch formal and idealistic rules and procedures to the breaking point. And yet, people in a variety of fields work through such difficulties in a pragmatic manner, at times finding ways to assert their humanity. Sensemaking and human- centred design are related activities through which many people approach such work. Through cases in digital innovation, global health care delivery and an unlikely voyage of the Amazon River, this portfolio shows that they are relevant to a wide range of settings. Rather than isolating the components or key variables of such work and taking their measure, this research advances a more holistic view of sensemaking and designing as sociomaterial practices. My research is grounded in performing the phenomenon of study, offering insights from complex practice rather than a spectator’s study of it. This ethnographic approach has yielded theoretical contributions related to designing for the emergence of practices, embodied sensemaking, a more substantive notion of what it means to be ‘human’ centred and more pragmatic ways of investigating sociomaterial practices. By discussing sensemaking and human-centred design as antidotes to failures of imagination in global health and development, this dissertation suggests a distinctive perspective on why these topics matter for the health of poor and marginalized people around the world.