The Zygophyllaceae subfamily Zygophylloideae includes seven genera and around 180 species distributed worldwide particularly in arid areas where they show various adaptations to drought including C4 and CAM photosynthesis. Phylogenetic relationships of Zygophylloideae have been analysed in several studies using Sanger sequenced markers, but deeper relationships between clades have remained recalcitrant. Here, we use ion semi-conductor sequencing of chloroplast and nuclear ribosomal regions to analyse these relationships and assess why they have proved so challenging to resolve. We analyse new data for 39 chloroplast genes and nuclear ribosomal 18S, 5.8S, and 26S gene and internal transcribed spacers for key species of Zygophyllum sensu stricto, Roepera, Tetraena, Fagonia, Zygophyllum stapffii and monotypic Augea capensis; and Tribulus of the subfamily Tribuloideae as outgroup, compared this to published chloroplast genomes, summarising phylogenetic results separately from non-coding introns and intergenic spacers, photosynthetic genes and non-photosynthetic genes. We combined this data with sequences of three highly variable noncoding chloroplast regions and ITS used in previous studies of greater numbers of taxa and assessed the effect on phylogenetic inference. We used a chloroplast sequence matrix to infer a dated phylogeny. Adding data did not always improve phylogenetic resolution which was impacted by non-informative variation in chloroplast photosynthesis related genes as well as by conflicting chloroplast and nuclear signals. This provides evidence for both selection and introgressive hybridization and/or incomplete lineage sorting during an ancient rapid divergence that will require multiple independent, informative, and neutral gene trees to resolve.