Rheumatoid arthritis (RA) patients with chronic kidney failure are intolerant to most disease-modifying antirheumatic drugs (DMARDs) and NSAIDs due to their potential toxicities. Although the tumor necrosis factor (TNF) inhibitors have emerged as a highly effective treatment for RA, their safety and efficacy in RA patients with chronic kidney failure have not been well reported. We retrospectively evaluated the safety and efficacy of etanercept treatment in RA patients with chronic kidney failure. We describe three RA patients with chronic kidney failure who had been treated with DMARDs, steroids and NSAIDs, but were discontinued from these classical agents due to several side effects and nephrotoxicity. The patients were treated with 25 mg of etanercept once or twice a week. We evaluated disease activity and used decreasing renal function and increasing number of infections to monitor safety. All three patients improved after starting etanercept treatment and their steroid requirements were decreased. Linear relationships between Modification of Diet in Renal Disease study equation (MDRD) glomerular filtration rate (GFR) and time were observed. Thus, in all patients, the changes in GFR did not represent superimposed acute drug toxicity, but rather chronic progressive renal failure. These cases show that etanercept may be a safe and effective treatment option for RA patients with chronic kidney failure.