Although recognized by the US government, Indigenous communities continue to be significantly under-funded, under-developed, and/or under-resourced. This dearth of support contributes to insufficient organizational infrastructure and capacity in a number of areas, creating challenges for American Indian, Alaska Native, Native Hawaiian, and Pacific Islander communities to thrive as equals with other US populations. This chapter describes three areas of infrastructure critical to operating health programs, including structures, workforce, and quality improvement. Examples are provided of community-engaged, infrastructure-strengthening programs undertaken by the Intertribal Council of Michigan, the Bad River Band of the Lake Superior Tribe of Chippewa Indians, a consortium of tribal communities in Arizona, the Alaska Native Tribal Health Consortium, and the INSPIRE program in American Samoa.