This is the first installment of a revision of the didelphid marsupial genus Philander, commonly known as gray four-eyed opossums. Although abundant and widespread in lowland tropical forests from southern Mexico to northern Argentina, species of Philander are not well understood taxonomically, and the current literature includes many examples of conflicting species definitions and nomenclatural usage. Our revision is based on coalescent analyses of mitochondrial gene sequences, phylogenetic analyses of mitochondrial and nuclear genes, morphometric analyses, and firsthand examination of relevant type material. Based on these results, we provisionally recognize eight species, of which three are formally treated in this report: P. quica (Temminck, 1824), an Atlantic Forest endemic formerly known as P. frenatus (Olfers, 1818); P. canus (Osgood, 1913), a widespread species formerly treated as a synonym or subspecies of P. opossum (Linnaeus, 1758); and P. pebas, a new species endemic to Amazonia. The remaining, possibly valid, species of Philander can be allocated to two clades. The first is a cis-Andean complex that includes P. andersoni (Osgood, 1913); P. mcilhennyi Gardner and Patton, 1972; and P. opossum. The second is a trans-Andean complex that includes P. melanurus (Thomas, 1899) and P. pallidus (Allen, 1901). Among other nomenclatural acts, we designate a neotype for the long-problematic nominal taxon Didelphis superciliaris Olfers, 1818, and (in an appendix coauthored by Renate Angermann), we establish that Olfers' coeval binomen D. frenata is based on an eastern Amazonian type and is a junior synonym of P. opossum.