In the present review, we will discuss the historical development, as well as the present and potential future applications of all five FDA-approved biological anti-TNF-α agents (infliximab, adalimumab, etanercept, golimumab and certolizumab), which have led to major improvements for patients with RA and other autoimmune diseases, such as ankylosing spondylitis, Crohn’s disease, ulcerative colitis and psoriasis. Here, TNF is linked to Crohn disease.