Muscadine grape (Vitis rotundifolia var. rotundifolia) is a rare crop in that it has transitioned from a wild fruiting plant to a domesticated fruit within the past 150 years. Furthermore, this domestication process was carried out by just a few institutions that published copious records of the origin and traits of the first wild selections, goals and methods of the breeding programs, and the pedigrees of releases. We thus have a near complete record of the domestication of this interesting fruit crop. Early breeding efforts made use of fewer than a dozen wild selections, most of which were collected from the coastal plain of North Carolina and South Carolina. This narrow germplasm base has led to increasing levels of inbreeding in the most recent muscadine cultivar releases. To better understand the germplasm base of muscadine, the pedigrees of 54 muscadine cultivars released since 1970 were examined. Only 15 founders (founding clones) were identified that appeared in more than two cultivars, and five of these represent open pollination events that may not indicate the addition of new genetic material. By far the most used founder was ‘Scuppernong’, which appeared in 53 of 54 pedigrees and had an average genetic contribution of 22.8%. The remaining founders varied from 0.9% to 14.8% in their average genetic contribution. Coancestry coefficients between cultivars averaged 0.18, but were often much higher among recent fresh-market releases. Analysis of vine vigor as measured by trunk caliper in seedling progenies suggests that coancestry coefficients greater than 0.23 result in below average seedling vigor. The University of Georgia muscadine breeding program is evaluating multiple wild muscadine accessions to reduce inbreeding and increase the genetic diversity of its germplasm.