Influenza continues to baffle humans by its constantly changing nature. The twenty-first century has witnessed considerable advances in the understanding of the influenza viral pathogenesis, its synergy with bacterial infections and diagnostic methods. However, challenges continue: to find a less expensive and more reliable point-of-care test for use in developing countries, to produce more efficacious antiviral drugs, to explore ways to combat emerging antiviral resistance and to develop vaccines that can either be produced in a shorter production time or can overcome the need for annual matching with the circulating influenza strains. Most importantly for India, as a nation that suffered the highest mortality in the influenza pandemic 1918, there is an urgent need to gear up our existing preparedness for the next pandemic which is capable to hit at any moment in time.