Influenza, a highly contagious respiratory tract infection, affects millions of adults and children each year. Several high-risk populations include children, the elderly, the immunocompromised, and recently the obese. Given the dramatic rise in obesity over the past few decades, this increased risk for influenza infection poses a serious public health threat because nearly 500 million adults and children worldwide are classified as obese. Obesity impairs the immune response to influenza and influenza vaccination through alterations of the cellular immune system. Compared with vaccinated healthy-weight adults, vaccinated obese adults have twice the risk of influenza or influenza-like illness despite equal serological response to vaccination. This challenges the current standard of protection for influenza and suggests that further vaccination methods or therapeutics are required to combat this virulent respiratory virus.