New World members of the Gobiesocinae (including Acyrtops, Acyrtus, Arcos, Derilissus, Gobiesox, Pherallodiscus, Rimicola, Sicyases, and Tomicodon) exhibit a heterodont oral dentition comprising two, and in some cases three, different types of teeth. The oral jaw teeth of New World gobiesocines are arranged in a series of 2–4 short staggered rows along the anterolateral margin of the premaxilla and dentary, to which new teeth are added posteriorly (rows 1–4) via shallow open crypts located along the labial margin of the jaw bones and medially (row 1 only) via one or two shallow open crypts located adjacent to the jaw symphysis. A putative monophyletic group comprising solely the New World genera of the Gobiesocinae is hypothesized based on characters of tooth arrangement and replacement in the oral jaws. The phylogenetic position of Eckloniaichthys, a homodont and the only Old World member of the Gobiesocinae, is discussed. The mode of tooth attachment in the Gobiesocidae is Type 2 (i.e., ring of collagen between tooth base and bone of attachment), and the mode of tooth replacement in the oral jaws is interpreted as intermediate between intraosseus and extraosseus replacement (sensu Trapani) and to take place in association with an internal cavity along the jaw bones.