Long-tongued horse flies (Diptera : Tabanidae : Pangoniinae) have proboscis lengths at least as long as their heads, the longest belonging to the Old World genus Philoliche (Wiedemann, 1820). These long proboscides are used to probe for nectar in deep-throated flowers. For some flower species, these flies are the only known pollinators. Although horse flies are both vectors of disease and important pollinators, there has been no previous study of phylogenetic relationships below the subfamily level. The first comprehensive phylogenetic hypothesis for Philoliche (and consequently, Tabanidae) based on molecular data from one nuclear (CAD) and one mitochondrial (COI) gene is presented here. Using an exemplar approach, species from eight of nine tribes in all three subfamilies in Tabanidae were sampled, giving some of the first insights into relationships among the family as a whole. All nine subgenera of Philoliche, and multiple geographic representatives of the subgenus P. (Philoliche) (Wiedemann, 1820) in southern Africa were also sampled. Within the subgenus Philoliche, molecular support was found for a previously synonymised species. In general, these analyses sustain earlier intuitive classifications, but do not support the monophyly of all currently recognised subfamilies.