Flowering dogwood (Cornus florida L.) populations have experienced severe declines caused by dogwood anthracnose in the past three decades. Mortality has ranged from 48 to 98%, raising the concern that genetic diversity of this native tree has been reduced significantly. Microsatellite data were used to evaluate the level and distribution of genetic variation throughout much of the native range of the tree. In the first conducted study, we found that genetic variation in areas affected by anthracnose was as high as or higher than areas without die-offs. We found evidence of four widespread, spatially contiguous genetic clusters. However, there was little relationship between geographic distance and genetic difference. These observations suggest that high dispersal rates and large effective population sizes have so far prevented rapid loss of genetic diversity. The effects of anthracnose on demography and community structure are likely to be far more consequential than short-term genetic effects. The second study examined levels and distribution of genetic variation of C. florida throughout Great Smoky Mountains National Park (GSMNP). Significant genetic structure at both landscape and local levels were found. We infer that two genetic clusters exist within the park, mostly separated by the main dividing ridge of the Great Smoky Mountains. The differentiation is statistically significant, but subtle, with gene flow evident through low-elevation corridors. It seems unlikely that recent demographic dynamics have resulted in a depletion of genetic variation in flowering dogwoods.