Influenza causes significant morbidity and mortality each year. Rapidly emerging influenza viruses resistant to available agents are a major cause for concern. Two classes of antivirals—adamantanes and neuraminidase inhibitors—are used in chemoprophylaxis and treatment of influenza. Although clinicians are under increasing pressure to prescribe antivirals for their patients, especially in the midst of the 2009 H1N1 pandemic, many flu viruses over the past few years have become resistant to these agents. To explain this phenomenon, the author discusses the biology of influenza viruses and the history of and causes for resistance to antiviral agents. The goal is for nurse practitioners to have a better understanding of the diagnosis, treatment, and prevention of influenza to better care for their patients during this 2009-2010 influenza season.