In annual epidemics and occasional pandemics, influenza viruses cause acute respiratory illnesses in infected humans. Vaccines and antiviral drugs are two main arsenals available for a fight against influenza viruses. However, vaccines often exhibit a limited efficacy in high risk populations, and antiviral drugs are always concerned for mutations, which confer viral resistance. Here we review current advances and knowledge in relation to the usage of antiviral drugs as a prophylactic or therapeutic and the mechanism of resistant variants mainly against the neuraminidase inhibitors. Comprehensive understanding of the resistant mechanism will pave a road for developing new antivirals and/or finding medical or natural alternatives inducing less frequent resistance, and application of combination therapy using two or three different kinds of antivirals can suggest a useful medical intervention against both of seasonal and highly pathogenic influenza viruses including resistant variants. In this review, we provide insights of antiviral drugs for the control and prevention of influenza viruses.