Influenza is an acute respiratory infection caused by influenza viruses (IFV), According to the World Health Organization (WHO), seasonal IFV epidemics result in approximately 3-5 million cases of severe illness, leading to about half a million deaths worldwide, along with severe economic losses and social burdens. Unfortunately, frequent mutations in IFV lead to a certain lag in vaccine development as well as resistance to existing antiviral drugs. Therefore, it is of great importance to develop anti-IFV drugs with high efficiency against wild-type and resistant strains, needed in the fight against current and future outbreaks caused by different IFV strains. In this review, we summarize general strategies used for the discovery and development of antiviral agents targeting multiple IFV strains (including those resistant to available drugs). Structure-based drug design, mechanism-based drug design, multivalent interaction-based drug design and drug repurposing are amongst the most relevant strategies that provide a framework for the development of antiviral drugs targeting IFV.