Avian influenza continues to evolve as a zoonotic threat with important implications for clinical practice and global health preparedness. Sustained circulation in wild birds, repeated spillover into poultry, and an increasing number of infections across diverse mammalian hosts have reshaped exposure pathways and broadened the risk landscape for human infection. For clinicians, this evolving ecology translates into atypical presentations and increased diagnostic uncertainty. Recent global activity has been characterised by widespread animal outbreaks and the emergence of new transmission interfaces, including occupational exposures and livestock-associated events. Human infections remain largely zoonotic and geographically heterogeneous, with patterns influenced by surveillance intensity, exposure context, and healthcare access. We synthesise current evidence on the virology, transmission, global epidemiology, clinical manifestations, diagnosis, treatment, and prevention of avian influenza in humans. We highlight evolving mammalian adaptation and changing risk interfaces that complicate risk assessment. Improved clinician awareness, early diagnosis, and integrated One Health surveillance remain central to strengthening preparedness for future influenza threats.