Most Neotropical crops were domesticated and have continued to be cultivated within the geographic ranges of their wild progenitors, so gene flow, in both directions, has been possible over millennia. The outcome of this gene flow is influenced by the strength and direction of selection, both natural and human. After domestication, crops spread into the ranges of other wild populations, adapted to somewhat different environmental factors. Selection remained important, but traits of the domestication syndrome, once fixed in the crop population, affected the rates and consequences of gene flow, again in both directions. Plant breeders have now overcome barriers of geographic isolation and, to an increasing extent, those of sexual incompatibility, so genes from wild species never previously encountered by the crop have been introduced into the crop gene pool, sometimes with unexpected consequences. These introductions may include artificially produced “designer genes,” unknown in the wild. Continued gene flow may enable alien genes (transgenes) to spread back into wild species, with potential consequences for both genetic diversity in the wild species and biodiversity in the ecosystem as a whole. Gene flow in each crop–wild species complex therefore needs to be investigated as a special case.