We examine the extent to which adult helminths of freshwater fishes have been part of the Great American Biotic Interchange (GABI), by integrating information in published studies and new data from Panama with fish biogeography and Earth history of Middle America. The review illustrates the following: (1) the helminth fauna south of the Trans-Mexican Volcanic Belt, and especially south of the Isthmus of Tehuantepec, shows strong Neotropical affinities; (2) host-parasite associations follow principles of the 'biogeographic core fauna' in which host-lineage specificity is pronounced; (3) phylogenetic analysis of the widespread freshwater trematode family Allocreadiidae reveals a complex history of host-shifting and co-diversification involving mainly cyprinodontiforms and characids; (4) allocreadiids, monogeneans and spiruridan nematodes of Middle American cyprinodontiforms may provide clues to the evolutionary history of their hosts; and (5) phylogenetic analyses of cryptogonimid trematodes may reveal whether or how cichlids interacted with marine or brackish-water environments during their colonization history. The review shows that 'interchange' is limited and asymmetrical, but simple narratives of northward isthmian dispersal will likely prove inadequate to explain the historical biogeography of many host-parasite associations in tropical Middle America, particularly those involving poeciliids. Finally, our study highlights the urgent need for targeted survey work across Middle America, focused sampling in river drainages of Colombia and Venezuela, and deeper strategic sampling in other parts of South America, in order to develop and test robust hypotheses about fish-parasite associations in Middle America.