The use of early aggressive treatment combined with the availability of biological agents targeting pro-inflammatory cytokines such TNF and IL-6 has greatly advanced the treatment of rheumatoid arthritis (RA). Clinical remission is a realistic primary goal and its maintenance leads to stabilisation of structural deterioration and functional remission. With the achievement of sustained remission, discontinuation of biological agents has emerged as an important consideration, with subsequent reductions in medication-induced side effects and health costs. Evidence from studies suggests that MTX-naïve, early RA patients can achieve sustained biologic-free remission with no functional or radiographic progression, after treatment with combination TNF inhibitors and MTX. For patients with long-standing RA and who have previous inadequate responses to MTX, the evidence for sustained biologic-free remission is less convincing. The discontinuation of TNF-inhibitors after sustained remission has been shown to be possible in some long-standing RA patients with inadequate response to MTX, particularly in Japanese patients. However, high flare rates and adverse long-term outcomes have been documented in other studies. For these patients a biologic dose-reduction regimen may be preferable. The combination of early treatment with TNF inhibitors and MTX plus tight control of inflammation provide the best chance of a biologic-free remission or at least the possibility of 'biologic treatment holidays'.