Next-generation genomic sequencing promises to quickly and cheaply resolve remaining contentious nodes in the Tree of Life, and facilitates species-tree estimation while taking into account stochastic genealogical discordance among loci. Recent methods for estimating species trees bypass full likelihood-based estimates of the multi-species coalescent, and approximate the true species-tree using simpler summary metrics. These methods converge on the true species-tree with sufficient genomic sampling, even in the anomaly zone. However, no studies have yet evaluated their efficacy on a large-scale phylogenomic dataset, and compared them to previous concatenation strategies. Here, we generate such a dataset for Caenophidian snakes, a group with >2500 species that contains several rapid radiations that were poorly resolved with fewer loci. We generate sequence data for 333 single-copy nuclear loci with ∼100% coverage (∼0% missing data) for 31 major lineages. We estimate phylogenies using neighbor joining, maximum parsimony, maximum likelihood, and three summary species-tree approaches (NJst, STAR, and MP-EST). All methods yield similar resolution and support for most nodes. However, not all methods support monophyly of Caenophidia, with Acrochordidae placed as the sister taxon to Pythonidae in some analyses. Thus, phylogenomic species-tree estimation may occasionally disagree with well-supported relationships from concatenated analyses of small numbers of nuclear or mitochondrial genes, a consideration for future studies. In contrast for at least two diverse, rapid radiations (Lamprophiidae and Colubridae), phylogenomic data and species-tree inference do little to improve resolution and support. Thus, certain nodes may lack strong signal, and larger datasets and more sophisticated analyses may still fail to resolve them.