Prednisone is an old and very valuable drug in clinical use for over 60 years by now. It is well known by physicians and widely used for different kinds of inflammatory states including rheumatoid arthritis (RA). Clinical trials during the last 20 years have changed its clinical use, particularly with regards to dosage. Today, rheumatologists are treating their patients much more likely over a long period of time using a low-dose scheme. The effectiveness and safety of this low-dose use is the objective of the current clinical research and shall be enlightened in this drug profile. It is also featuring current knowledge about the value of modified-release prednisone with regards to the just published results of the 2nd Circadian Administration of Prednisone in Rheumatoid Arthritis trial. Moreover, the mechanisms of action of prednisone and its relatives will be summed up.