The orthopedic community has learned much about the treatment of open fractures from the tremendous work of Ramon Gustilo, Michael Patzakis, and others; however, open fractures continue to be very difficult challenges. Type III open fractures continue to be associated with high infection rates. Some combination of systemic and local antibiotics may be most appropriate in these high-grade open fractures. Further research is still necessary in determining optimal systemic antibiotic regimens as well as the role of local antibiotics. Any new discoveries related to novel systemic antibiotics or local antibiotic carriers will need to be evaluated related to cost.