Enveloped animal viruses fuse their membrane with a host cell membrane in order to deliver their genome into the cytoplasm of the cell and thus initiating infection. This crucial step is mediated by virally encoded transmembrane proteins that, following an appropriate triggering, insert their fusion peptides into the target membrane and, through a cascade of conformational changes, drive the merging of the two apposing membranes. The battle against viruses is ongoing with the constant threat of viruses developing resistance to present drugs and emerging viruses, therefore there is a continuous challenge to improve our defence strategies. Entry inhibitors are currently in development for diverse human and animal viral pathogens, and advances in our understanding on how viral entry proteins undergo conformational changes that lead to entry offer a huge potential for the development of novel therapeutics. This review describes recent advances on viral-mediated fusion mechanisms concentrating on the development of peptidic inhibitors of membrane fusion.