Immunomodulators and biological agents are effective for the treatment of ulcerative colitis and Crohn's disease; however, there is concern that these therapies may be associated with an increased risk of malignancy. MEDLINE, Cochrane Library, and Web of Science were searched for articles regarding these medications and their associations with hematologic malignancies and solid tumors in inflammatory bowel diseases (IBDs) and transplant, rheumatology, dermatology, and neurology patient populations. There is evidence that use of thiopurines and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of lymphoma, particularly non-Hodgkin's lymphoma in patients with IBD. Hepatosplenic T-cell lymphoma, although rare, also occurs with increased frequency in patients treated with thiopurines and anti-TNF medications, and young male patients with Crohn's disease appear to be at greatest risk. Furthermore, thiopurines and anti-TNF agents are associated with elevated rates of nonmelanoma skin cancer in non-IBD and IBD patients, and anti-TNF agents may also increase the risk of melanoma. Rates of abnormal cervical cytology may be elevated by the use of immunosuppressive agents in female patients with IBD. There is little evidence that exposure to the therapeutic agents prescribed for IBD increases the risk of any other solid tumors or hematologic malignancies in non-IBD or IBD patients. Although the use of immunomodulators and anti-TNF agents can promote certain types of lymphoma and skin cancer, patients and clinicians should be aware that the absolute rates of these malignancies remain low, and these risks should be weighed carefully against the substantial benefits offered by these therapies.