Abstract: The outbreak of the influenza viruses (IFV) caused significant harm to our health and life. Human infections caused by pathogenic avian influenza virus (AIV) have continually brought great panic and death threats to people all over the world. With the in-depth study of the biological characteristics of influenza viruses and the rapid development of drug discovery screening technology, a new generation of anti-influenza drug targets and their inhibitors have been continuously discovered, providing more options for the treatment of influenza. From the point of view of medicinal chemistry, this review summarizes and discusses current endeavours towards the discovery and development of novel inhibitors and also provides examples illustrating new methodologies that contribute to the identification of novel anti-influenza drugs.