The polygrammoid fern family Polypodiaceae represents one of the most diversified epiphytic fern groups, with more than 1600 species distributed on all continents except Antarctica, with the highest species diversity in tropical and subtropical regions. Despite progress in recent phylogenetic studies of Polypodiaceae, the infrafamilial classification of this group of ferns is still problematic. Here, we explore the phylogenetic relationship within Polypodiaceae using plastid genome (plastome) and nuclear ribosomal cistron genome data obtained from high-throughput sequencing. Although genome skimming data strongly support the monophyly of many genera and clades of Polypodiaceae, relationships within some clades and along the backbone of the phylogeny remain incongruent between plastome and nuclear data. The explanation is possibly a factor of complex evolutionary history found in these clades, such as rapid radiation, incomplete lineage sorting, ancient hybridization, and recent introgression. Based on the concatenated dataset, our phylogenetic analyses support nine major clades in Polypodiaceae, which merit the recognition as subfamilies, Crypsinoideae, Grammitidoideae, Loxogrammoideae, Microsoroideae, Platycerioideae, Polypodioideae, Adetogrammoideae, Campyloneuroideae, and Serpocauloideae, while the latter three are separated from Polypodioideae as new subfamilies. All of these infrafamilial divisions, identified with molecular data, are further supported by non-molecular features including leaf dissection, venation, scales and paraphyses, soral features, and geographical distributions. Systematic and taxonomic discussions on the subfamilial treatment are also provided.