Paradrymonia Hanst. (Gesneriaceae) with 40 currently recognized species is a genus of facultative epiphytic herbs that inhabits the forest understory. The genus occurs throughout the Neotropics except for southeastern Brazil and the Caribbean. Monophyly of neotropical Paradrymonia and species relationships within the genus and closely related genera were evaluated based on molecular sequence data from the nuclear ribosomal (nrDNA) internal and external transcribed spacer regions (ITS and ETS), and the plastid (cpDNA) psbA-trnH intergenic spacer. Traditional Paradrymonia is resolved as polyphyletic and includes taxa in three clades. The clade that contains the type species is recognized as Paradrymonia sensu stricto (s. s.) and includes three species. The Paradrymonia s. s. clade is sister to a clade that includes species of Nautilocalyx, Chrysothemis, and most of the species traditionally recognized as Paradrymonia. Morphological characters useful for circumscribing generic boundaries include bearded anthers, rosette habit, presence of leaf anisophylly, and lanceolate calyx lobe shape. Our results support the re-circumscription of Paradrymonia and the resurrection of two previously recognized genera, Centrosolenia and Trichodrymonia, in order to accommodate the remaining ex-Paradrymonia species. Forty-three new combinations (11 in Centrosolenia, four in Chrysothemis, and 28 in Trichodrymonia) are made. The genus Nautilocalyx is moderately supported as lacking monophyly, but broader taxon sampling is necessary before new generic circumscriptions are provided.