Over the past 25 years, there has been an increasing number of mammalian (including human) infections caused by avian influenza A viruses that resulted in mild to severe illnesses. These viruses typically did not spread between mammals through aerosols in nature or in experimental settings. However, recently, this has changed, with several avian influenza A viruses exhibiting aerosol transmissibility among mammals, indicating that these viruses may pose a greater pandemic risk. In this review, we examine the current situation and discuss the mutations that may be necessary for avian influenza A viruses to efficiently replicate in mammals and transmit among them via aerosols.