This resource is a guide to amplify global health impact from the perspective of a development organisation. It builds on the successes of USAID's work and lays out practical ways to identify opportunities to apply innovation to solve real problems using a portfolio approach. The resource has been co-developed with significant input from USAID colleagues across their health offices, and captures best practices and innovation opportunities, dispels myths and highlights examples of and resources for innovation in global health. Though this guide is primarily intended for USAID staff, it can serve as an adaptable resource for other organisations as well as beyond the health field.