Annual influenza epidemics and periodic pandemics result in excess hospital admissions. Hospitalization typically occurs in those with underlying medical conditions, those at the extremes of age and in pregnant woman; young adults and obese individuals were also at increased risk during the 2009 H1N1 pandemic. Severe influenza pneumonia, exacerbation of underlying lung diseases, cardiovascular and cerebrovascular events and bacterial superinfection are common reasons for hospitalization. Clinical diagnosis is unreliable and virological confirmation can be challenging. Overall mortality among adults hospitalized with influenza ranges from 4% to 8%, although higher mortality (>10-15%) may be seen during pandemics and among the immunocompromised. Recent data have suggested that neuraminidase inhibitors, particularly when given early, can accelerate viral clearance and improve clinical outcomes in hospitalized adults; thus, antiviral treatment should be considered in all cases. Controlled clinical trials are urgently needed in this population to evaluate comparative treatment efficacy of different agents and combinations, including emergence of antiviral resistance, and to address issues related to dosage, duration and parenteral route.