Species of Hoffmannia Sw. (Rubiaceae, Hamelieae) are concentrated in premontane and montane areas of Central America and southern Mexico and are notably variable morphologically, but are here treated as less variable than some previous authors have concluded. In particular, corolla shape and color and fruit shape are here considered species-level characteristics, and leaf shape and inflorescence size and position are considered less variable than previously posited. Fourteen species new to science have been discovered by recent exploration in Central and South America and are described here. One group of species includes Hoffmannia plants from Nicaragua, Costa Rica, Panama, and northwestern Colombia with paired ant vesicles (i.e., formicaria) at the base of each leaf blade. These plants have recently been all included in one species, H. vesiculifera Standl., but two other previously described species are recognized here, H. morii Dwyer and H. kirkbridei Dwyer, along with five newly described species and all the Hoffmannia species with ant vesicles are keyed here. The newly described Hoffmannia species with ant vesicles on their leaves are: H. formicaria C. M. Taylor of Costa Rica and western Panama, which differs from H. morii by its pedunculate inflorescences, pedicellate flowers, and white, greenish yellow, or pink corollas; H. limonensis C. M. Taylor of Costa Rica and western Panama, which differs from H. vesiculifera by its corollas with the acute to acuminate lobes longer than the tube; H. pseudovesiculifera C. M. Taylor of western Panama, which differs from H. vesiculifera by its scorpioid inflorescences and corollas with the lobes longer than the tube and in general unusually long within the genus; H. subcapitata C. M. Taylor of Costa Rica, which differs from H. kirkbridei by its shorter petioles, subcapitate pedunculate inflorescences, and longer broader calyx lobes; and H. veraguensis C. M. Taylor of western Panama, which differs from H. formicaria by its shorter calyx lobes and smaller corollas. The remaining Hoffmannia species newly described here lack ant vesicles on the leaves: H. barbillana C. M. Taylor of Costa Rica differs from H. longipetiolata Pol. in its sessile leaves that are rounded at the base and its epiphytic habit; H. boliviana C. M. Taylor of Bolivia and Peru differs from H. obovata (Ruiz & Pav.) Standl., H. latifolia (Bartl. ex DC.) Kuntze, and H. pearcei Rusby in its longer petioles, broader leaves, and smaller flowers; H. coriacea C. M. Taylor of central Peru is distinguished within Hoffmannia by its narrow leathery leaves and corolla with the tube longer than the lobes; H. costaricensis C. M. Taylor of Costa Rica differs from H. valerioi Standl. in its shorter calyx lobes and oblanceolate leaves; H. micrantha C. M. Taylor of Costa Rica differs from H. hammelii C. M. Taylor by its orange, brown, or purple corollas that are acute in bud; H. pacifica C. M. Taylor of Costa Rica is distinguished from H. hammelii by its subsessile leaves that are rounded to cordulate at the base; H. rivalis C. M. Taylor of lowland Peru is distinguished by its rheophytic habit, densely pubescent stems, narrow leaves, and small flowers; H. tilaranensis C. M. Taylor of Costa Rica differs from H. nicotianifolia (M. Martens & Galeotti) L. O. Williams in its larger red to purple flowers and larger leaves; and H. turrialbana C. M. Taylor of Costa Rica is distinguished from H. pittieri Standl. by its subsessile leaves that are truncate to cordulate at the base and have numerous secondary veins plus its few-flowered racemiform inflorescences.