With the evolution of therapies for RA, new treatment strategies and goals of therapy have evolved. Recent European League Against Rheumatism (EULAR) guidelines on the treatment of RA proposed three phases of therapy: phase I comprising first-line synthetic DMARD with or without glucocorticoid; phase II comprising second-line synthetic DMARD with or without glucocorticoid, or combination synthetic DMARD therapy, or (if prognostic factors are poor) first-line biologic DMARD; and phase III comprising alternative biologic DMARDs. In all phases, the key principle is tight control: striving to achieve a predefined goal of remission or low disease activity (treat to target) with frequent dose and medication adjustments tailored to the individual patient, preferably within the window of opportunity during early RA. In all phases, MTX is recognized as an anchor drug; it is characterized by proven efficacy in combination DMARD strategies, relatively low cost, relatively rapid onset of action, proven beneficial impact on radiological progression and mortality and a wide dose range that facilitates dose adjustments. Prednisone and its active metabolite, prednisolone, have similar characteristics, making them ideal anchor drugs too. The EULAR guidelines reserve a place for MTX and glucocorticoids in all phases of treatment. The second CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) study in early RA has demonstrated that including prednisone from the start in an MTX-based tight control strategy aimed at remission improves disease activity variables, time to remission, functional disability and radiological joint damage compared with the same strategy without prednisone. In conclusion, both MTX and prednisone play key roles in modern RA treatment strategies.