Tumor necrosis factor (TNF) inhibitors are being increasingly utilized in the management of inflammatory bowel disease (IBD). Although the benefits associated with TNF inhibitor therapy are undeniable, concerns have been raised about the associated risk of infectious and malignant complications. In this narrative review, we will present the evidence from studies that have evaluated the association of TNF inhibitors and both overall and specific infections and malignancy. Overall, although TNF inhibitors may increase the risk of tuberculosis, varicella, and other opportunistic infections, there is little evidence suggesting that anti-TNF agents specifically raise the overall risk of serious infections. Similarly, there is little evidence that TNF antagonists raise the risk of developing malignancy over and above the risks from concomitant therapies and the underlying disease process. However, the risk of nonmelanoma skin cancers may be increased and that is further enhanced by use of combination TNF inhibitor and thiopurine therapy. The risk of non-Hodgkin's lymphoma is statistically increased among combination therapy users. The absolute risk remains a very small but feared risk. It is difficult to fully quantify the risk of these cancers among users of TNF inhibitor therapy in the absence of concurrent thiopurine therapy. We recommend that clinicians remain mindful about the potential risks of infectious and malignant complications in their IBD patients who are using TNF inhibitors, but that further research is required to better study these risks over the long-term course of therapy.