Over the last decade, the medical treatment of inflammatory bowel disease (IBD) has been revolutionized, with increasing use of both immunomodulatory and biologic medications. Corticosteroids have increasingly been shown to increase the risk of serious and opportunistic infections, both independently and in combination with immunomodulator and biologic agents. There are limited data on the infectious risk of immunomodulators. It is unclear if anti-tumor necrosis factor-alpha agents increase overall infectious risk in patients with IBD, but the available literature has demonstrated an increased risk of opportunistic infections, particularly in terms of tuberculosis and histoplasmosis. Combination therapy likely increases the risk of opportunistic infections in patients with IBD but this has not yet been conclusively proved.