The phylogenetic relationships of Mertensia (Boraginaceae), which comprises approximately 45 species in both Asia and North America, have been uncertain, and taxonomists have placed the genus in various tribes of subfamily Boraginoideae, with the most recent placements in Trigonotideae and Cynoglosseae. Our study applies molecular phylogenetic methods to test the monophyly and relationships of Mertensia. We used DNA sequence data from the nuclear ribosomal nrITS region and four cpDNA regions (matK, ndhF, rbcL, trnL-trnF) to examine the placement of Mertensia among a sampling of accessions from approximately 70% of the genera of Boraginaceae s. l. Phylogeny reconstructions using maximum parsimony, maximum likelihood, and Bayesian inference were largely congruent with previous molecular phylogenetic analyses of Boraginaceae that had applied far fewer taxa. We recovered five deep clades that correspond to Boraginaceae subfamilies Boraginoideae, Cordioideae, Heliotropioideae, Hydrophylloideae, and Ehretioideae (including Lennoa and Pholisma). In subfamily Boraginoideae, we recovered clades that correspond to the tribes Echiochilieae, Lithospermeae, Cynoglosseae, and Boragineae, although several tribes previously circumscribed on the basis of morphological data were not recovered as monophyletic in our results. Based on the sister relationship between the genus Codon and subfamily Boraginoideae found in our phylogeny reconstructions, we propose Codoneae as a new tribe of Boraginoideae. We recovered strong support for the monophyly of Mertensia and the placement of the monotypic genus Asperugo as its sister. Mertensia and Asperugo were strongly supported as members of Cynoglosseae.