Aims: This article is designed to demonstrate the problems of infection in a time without antibiotics and to raise awareness and stimulate discussion about the future and the next steps for managing antibiotic resistance. Methods: Access was gained to original journals and letters of three doctors, who joined the army working as medical officers during the First World War. Transcripts of interviews of the doctors performed after the war, in 1977-1979, were also looked at. These original records were studied and any references to infection were collected. A literature search was then performed to identify research carried out during the First World War on the development of the management of infection and sanitation during that time period. A further literature search was then performed to identify modern day concerns with infection, in particular with regard to antibiotic resistance. Results: The three doctors made many comments about infection in their journals and letters written during the war. It was clearly a major concern in the treatment of injured soldiers and few effective remedies were available. The literature search demonstrated that this concern was worldwide with massive investment in research between 1915 and 1917. This produced a drive of innervation and development, rapidly improving the management of infection during that time. Now, with concerns of rising antibiotic resistance, infection is again becoming a medical challenge that requires a renewed drive to push research forward. Conclusions: This article demonstrates that without effective antibiotics infection is massive medical challenge. However when a problem is identified it is possible to produce rapid solutions with research and development. Antibiotic resistance is on the rise. Further research with international cooperation is now required to ensure a simple wound does not become untreatable condition.