To be effective, healthcare technologies should be attuned to particular contexts of use. This article examines how such attuning is articulated in global innovation practices for tuberculosis and HIV diagnostics, and to what effect. It examines the development of point-of-care (POC) diagnostics – promised to be designed for users outside laboratories or in resource constrained settings – to study what developers and implementers do to align diagnostic technologies to the POC. Fieldwork among global health actors involved in diagnostic development, including manufacturers, donors, industry consultants, international organizations, policymakers, regulators and researchers, is combined with fieldwork among users of diagnostics in India, including decision-makers, NGOs, program officers, laboratory technicians and nurses. The article adds to STS’s theory of alignment and user interaction, where the setting and user to which developers and implementers of global health diagnostics align are multiple, varied, emerging and keep shifting. The characteristics of a local user setting include multiple engaged and imagined user settings, but also the settings of developers, of global intermediaries, competitors and diseases. As such, alignment is happening across multiple dimensions and scales and has an important temporal dimension. The results reveal how alignment happens to some extent in the dark, characterized by uncertainty about the elements that should align. Standardizing elements, politics and scarce resources cause frictions in the temporalities of aligning and over what constitutes a well-aligned diagnostic.