With the development of biologicals that specifically target tumor necrosis factor (TNF)α, our therapeutic approach to inflammatory diseases has dramatically changed. There are currently three anti-TNFα drugs available: etanercept, infliximab, and adalimumab. Etanercept is a recombinant fusion protein that can be used alone or in combination with other medications for conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis. Infliximab, a chimeric humanized monoclonal antibody and adalimumab, a fully human monoclonal antibody are approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and moderate to severe Crohns disease. Infliximab is also approved for ulcerative colitis, adalimumab for juvenile rheumatoid arthritis. Another anti-TNFα drug, certolizumab pegol, was declined EMEA approval as treatment option for active Crohns disease . However, in the USA it was approved by the FDA to treat moderate to severely active Crohns disease in adults who have not been helped by usual treatments (April 2008) in addition to the treatment of moderately to severely active rheumatoid arthritis (May 2009). It is the goal of this review article to summarize various therapeutic indications, underlying studies, safety, and use during pregnancy, as well as future directions for anti-TNF therapies.