The world is now experiencing an epidemic of obesity. Although the effects of obesity on the development of metabolic and cardiovascular problems are well studied, much less is known about the impact of obesity on immune function and infectious disease. Studies in obese humans and with obese animal models have repeatedly demonstrated impaired immune function, including decreased cytokine production, decreased response to antigen/mitogen stimulation, reduced macrophage and dendritic cell function, and natural killer cell impairment. Recent studies have demonstrated that the impaired immune response in the obese host leads to increased susceptibility to infection with a number of different pathogens such as community-acquired tuberculosis, influenza, Mycobacterium tuberculosis, coxsackievirus, Helicobacter pylori and encephalomyocarditis virus. While no specific mechanism has been defined for the decreased immune response to infectious disease in the obese host, several obesity-associated changes such as excessive inflammation, altered adipokine signaling, metabolic changes and even epigenetic regulation could affect the immune response. This review will discuss what is currently known about the relationship between obesity and infectious disease.