The emergence of the 2009 H1N1 pandemic influenza A virus, as well as constant antigenic drift of seasonal influenza, underscores the remarkable versatility of this virus in adapting to the human population. While vaccines are the principal public health defence against influenza, rapid vaccine development can be a daunting task. Antiviral drugs offer the promise of inhibiting influenza regardless of its genetic variations. However, the rapid rise of resistance to several antivirals has highlighted the need for developing novel therapeutics with reduced drug resistance potential. In this review, we will summarize the effects of the currently licensed anti-influenza drugs as well as the candidates in development against the seasonal and the 2009 H1N1 pandemic influenza A virus with an emphasis on drug resistance.