Castilleja (Orobanchaceae) exemplifies a recent and rapid radiation of ca. 200 species that is associated with both perenniality and polyploidy. Chloroplast phylogenomics and limited multi-locus nuclear gene trees have revealed a pattern of historic and contemporary gene flow between morphologically distinct species that, along with a lack of phylogenetic signal in the relatively few nuclear genes that have been included in analyses to date, has hampered our ability to resolve genus-wide phylogenetic relationships. Here we use the Angiosperm353 probe set to greatly increase sampling of the nuclear genome and further clarify species relationships in Castilleja. In addition, we use a recently generated, chromosome-level genome of Castilleja foliolosa to formally assess orthology and identify paralogs in both diploid and polyploid Castilleja species.