Since the introduction of tumor necrosis factor (TNF)-α inhibitors, the treatment of rheumatoid arthritis (RA) has been revolutionized. The approach of targeting TNF-α has considerably improved the success in the treatment of RA. Over the last 3 decades five different TNF-α inhibitors have been administered: infliximab, etanercept, adalimumab, golimumab, and certolizumab-pegol. All of them show excellent efficacy with similar rates of clinical response and prevention of radiographic disease progression. With improved therapies, treatment strategies have also changed, with the aims now being to achieve and maintain remission. Most recently, the discussion expands to the issue of treatment reduction in patients who have achieved sustained remission; here, the discontinuation of TNF-α inhibitor therapy has become an area of interest, given obvious economic and risk-benefit evaluations. However, only little is known if “biologic free” remission is possible in patients with sustained remission following intensive TNF-α inhibitor therapy.