Summary: Resistance is an ongoing concern for all physicians, and it is important that judicious evidence-based prescribing be initiated in order to minimize the development of resistance. However, the benefits of appropriate treatment outweigh the disadvantages, with the benefits of prophylactic antimicrobial treatment in febrile neutropenia confirmed in randomized clinical trials. Therefore, it is important to ensure that treatment is given to appropriate patients. Those found to benefit from prophylactic antibiotic therapy include patients at high risk of developing neutropenia, those with a risk of developing either profound or long-lasting neutropenia, and those with significant underlying comorbidities that increase their risk profile.