Introduction: The emergence and spread of the pandemic H1N1 influenza virus in 2009 indicates a limitation in the strategy to control the infection, despite a long-established vaccination programme and approved antivirals. Production the proper vaccine against influenza is difficult due to the genetic recombination of virus in the event of pandemic and co-circulation of drug-resistance variants highlights the need for the development of new effective and broad-spectrum influenza therapies. Currently, the investigations lie on viral attachment and entry inhibitors, and more attention focuses on viral genome replication and transcription inhibitors in such a way that selective pressure applied by the use of antiviral drugs has covered against all strains. In this review, the novel antiviral agents that targeted the virus-cell membrane attachment, and transcription of the viral genome are discussed