Amblycipitidae Day, 1873 is an Asian family of catfishes (Siluriformes) usually considered to contain 28 species placed in three genera: Amblyceps (14 spp.), Liobagrus (12 spp.) and Xiurenbagrus (2 spp.). Morphology-based systematics has supported the monophyly of this family, with some authors placing Amblycipitidae within a larger group including Akysidae, Sisoridae and Aspredinidae, termed the Sisoroidea. Here we investigate the phylogenetic relationships among four species of Amblyceps, six species of Liobagrus and the two species of Xiurenbagrus with respect to other sisoroid taxa as well as other catfish groups using 6100 aligned base pairs of DNA sequence data from the rag1 and rag 2 genes of the nuclear genome and from three regions (cyt b, CO1, ND4 plus tRNA-His and tRNA-Ser) of the mitochondrial genome. Parsimony and Bayesian analyses of the data indicate strong support for a diphyletic Amblycipitidae in which the genus Amblyceps is the sister group to the Sisoridae and a clade formed by genera Liobagrus and Xiurenbagrus is the sister group to Akysidae. These taxa together form a well supported monophyletic group that assembles all Asian sisoroid taxa, but excludes the South American Aspredinidae. Results for aspredinids are consistent with previous molecular studies that indicate these catfishes are not sisoroids, but the sister group to the South American doradoid catfishes (Auchenipteridae Doradidae). The redefined sisoroid clade plus Bagridae, Horabagridae and (Ailia Laides) make up a larger monophyletic group informally termed “Big Asia.” Likelihood-based SH tests and Bayes Factor comparisons of the rag and the mitochondrial data partitions considered separately and combined reject both the hypothesis of amblycipitid monophyly and the hypothesis of aspredinid inclusion within Sisoroidea. This result for amblycipitids conflicts with a number of well documented morphological synapomorphies that we briefly review. Possible nomenclatural changes for amblycipitid taxa are noted.