Ovine footrot is a contagious and debilitating disease that is of major economic significance to the sheep meat and wool industries. The causative bacterium is the gram negative anaerobe Dichelobacter nodosus. Research that has used a classical molecular genetics approach has led to major advances in our understanding of the role of the key virulence factors of D. nodosus in the disease process. D. nodosus strains produce polar type IV fimbriae and extracellular serine proteases. Mutagenesis of the fimbrial subunit gene fimA and the pilT gene, which is required for fimbrial retraction, and subsequent testing of these mutants in sheep virulence trials has shown that type IV fimbriae-mediated twitching motility is essential for virulence. The extracellular protease genes aprV2, aprV5 and bprV have also been mutated. Analysis of these mutants has shown that ArpV5 is the major extracellular protease and that AprV2 is the thermostable protease that is responsible for the extracellular elastase activity. Structural analysis of AprV2 has revealed that it contains several novel loops, one of which appears to act as an exosite that may modulate substrate accessibility. Finally, virulence experiments in sheep have shown that the AprV2 protease is required for virulence.