The study combines phylogenetic analyses with protein structure prediction to survey glycoproteins across the *Flaviviridae* family, which includes viruses such as hepatitis C, dengue, and Zika. The authors identify class II fusion systems homologous to the Orthoflavivirus E glycoprotein in most species, including highly divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of hepaciviruses, pegiviruses, and pestiviruses are structurally distinct and may represent a novel class of fusion mechanism, strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny, the authors reveal a complex evolutionary history marked by the capture of bacterial genes and potentially inter-genus recombination. These insights, made possible through protein structure prediction, refine our understanding of viral fusion mechanisms and reveal the events that have shaped the diverse virology and ecology of the *Flaviviridae*.The study combines phylogenetic analyses with protein structure prediction to survey glycoproteins across the *Flaviviridae* family, which includes viruses such as hepatitis C, dengue, and Zika. The authors identify class II fusion systems homologous to the Orthoflavivirus E glycoprotein in most species, including highly divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of hepaciviruses, pegiviruses, and pestiviruses are structurally distinct and may represent a novel class of fusion mechanism, strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny, the authors reveal a complex evolutionary history marked by the capture of bacterial genes and potentially inter-genus recombination. These insights, made possible through protein structure prediction, refine our understanding of viral fusion mechanisms and reveal the events that have shaped the diverse virology and ecology of the *Flaviviridae*.