Santalaceae sensu stricto, the type family for the sandalwood order (Santalales), include approximately 40 genera and over 550 species distributed worldwide. Because the family possesses plesiomorphic and generalized traits that occur throughout the order, this diverse assemblage of hemiparasitic plants has been difficult to characterize and differentiate from related families. We present phylogenetic analyses of all genera of Santalaceae, as well as Viscaceae and selected Opiliaceae, using DNA sequences from nuclear small-subunit ribosomal DNA as well as the chloroplast genes matK and rbcL. The concatenated data set, analyzed with parsimony, likelihood, and Bayesian inference, gave congruent results, with the majority of clades fully resolved. Our results reveal that the family is polyphyletic and that the genera of Santalaceae, as traditionally classified, occur in nine well-supported clades. The South American herbaceous perennial genera Arjona and Quinchamalium are sister to Schoepfia (Schoepfiaceae). The Australian genus Anthobolus emerges as a member of Opiliaceae. Viscaceae remain intact and are well supported as monophyletic. The remaining genera included in Santalaceae occur in six well supported clades, but the relationships among these clades are not fully resolved. These clades are, based on a component generic name, Comandra, Thesium, Cervantesia, Nanodea, Santalum and Amphorogyne. Morphological features diagnostic of these clades are discussed with the intention that these results will serve as the foundation for a revised classification.