There is strong evidence indicating that excess adiposity negatively impacts immune function and host defence in obese individuals. This is a review of research findings concerning the impact of obesity on the immune response to infection, including a discussion of possible mechanisms. Obesity is characterised by a state of low-grade, chronic inflammation in addition to disturbed levels of circulating nutrients and metabolic hormones. The impact of these metabolic abnormalities on obesity-related comorbidities has undergone intense scrutiny over the past decade. However, relatively little is known of how the immune system and host defence are influenced by the pro-inflammatory and excess energy milieu of the obese. Epidemiological data suggest obese human subjects are at greater risk for nosocomial infections, especially following surgery. Additionally, the significance of altered immunity in obese human subjects is emphasised by recent studies reporting obesity to be an independent risk factor for increased morbidity and mortality following infection with the 2009 pandemic influenza A (H1N1) virus. Rodent models offer important insight into how metabolic abnormalities associated with excess body weight can impair immunity. However, more research is necessary to understand the specific aspects of immunity that are impaired and what factors are contributing to reduced immunocompetence in the obese. Additionally, special consideration of how infection in this at-risk population is managed is required, given that this population may not respond optimally to antimicrobial drugs and vaccination. Obesity impacts millions globally, and greater understanding of its associated physiological disturbances is a key public health concern.