Onagraceae are a family of 17 genera in seven tribes, with the majority of species in tribes Onagreae and Epilobieae. Despite the species-richness of these two tribes, to date no phylogenetic study has been done with sufficient taxon sampling to examine relationships between and within these tribes. In this study, we used DNA sequence data from one nuclear region (ITS) and two chloroplast regions (trnL-trnF and rps16) to infer phylogenetic relationships among 93 taxa across the family, with concentrated sampling in the large tribe Onagreae. Results strongly suggest that tribe Gongylocarpeae is sister to tribes Epilobieae Onagreae, both of which are monophyletic. Within Onagreae, Camissonia seems to be broadly paraphyletic, and Oenothera is also paraphyletic. In Oenothera there appear to be two lineages, one of which has Gaura Stenosiphon nested within it. At the base of the Onagraceae phylogeny, we have clarified previous confusion regarding conflicting placements of Hauya and Lopezia based on nuclear versus chloroplast data. Results of these analyses are supported by morphology and suggest the need for new taxonomic delimitations, which are forthcoming.