Premise of the study: The use of multiple genetic regions from the nuclear genome, including low-copy markers, has long been recognized as essential to robust phylogenetic construction, addressing gene tree incongruence, and allowing increased resolution to test current taxonomy and resolve basic hypotheses about character evolution, biogeography, and other organismal traits of interest to biologists. Heuchera, the largest genus of Saxifragaceae endemic to North America, has presented an unusually difficult case for systematists with limited sampling in previous molecular studies. We used morphological and multilocus molecular phylogenetic data to test the monophyly of Heuchera, better resolve hypotheses of relationships, and test hypotheses of character evolution, biogeography, and diversification rates. Methods: Phylogenetic relationships were inferred using sequences from six nuclear loci and 39 morphological characters using concatenation and coalescent analysis. Ancestral state reconstruction, diversification, and correlated evolution of morphological traits were performed using parsimony, BiSSE, and Pagel’s method, respectively. Key results: The concatenation and species tree analyses gave confident support to the monophyly of Heuchera and suggested several well-supported subclades. The addition of morphological data significantly improved support numbers. Ancestral character reconstruction suggested frequent homoplasy and reversal of floral characters and a complex biogeographical history. Conclusions: Heuchera is a natural genus; however, the current subgeneric classification is artificial and requires revision. Biogeographic reconstructions suggest a Pacific Northwest origin for the genus; morphological shifts in stamen exsertion and hypanthium length are hypothesized to have driven diversification in Heuchera in concert with possible pollinator shifts.