Mistletoes occur worldwide, with most relying on birds to disperse their sticky seeds to suitable host trees. There has been considerable ecological research on these interactions, emphasizing those birds dependent on mistletoe fruit as their principal food source, but the origins and evolutionary trajectories of these dietary specialists have rarely been considered. Of the ten lineages of mistletoe fruit specialists, five are from the Tyrannida infraorder of South American songbirds comprising mannakins, cotingas, tyrant flycatchers and allies. Integrating current understanding of early songbird evolution with dietary information, two sets of findings emerged. First; dependence on mistletoe fruit is conserved over time, with strong evidence that the 137 mistletoe-dependent species in ten groups scattered among Neotropical suboscines arose from a rapid radiation in the late Oligocene and early Miocene. Although interpreted as a single origin of mistletoe fruit dependency, the degree of dependence was dynamic, mistletoe fruit specialists evolving from more generalised mistletoe-dependent lineages on five separate occasions as they radiated into the Americas from Gondwanan connections. Second, variation in diversity of modern mistletoe specialist frugivores can be explained by lineage age. Considering both representatives from the neotropical groups evaluated here and the other five families across modern birds, mistletoe fruit specialists initially spread rapidly, colonising new areas and speciating, then eventually becoming restricted to single regions represented by relictual lineages with divergent morphologies. After exploring the historic basis, evolutionary implications and ecological relevance of these findings, I consider alternative explanations and articulate testable predictions to corroborate or refute these inferences and guide future work.