Colchicine is the only drug known to effectively prevent familial Mediterranean fever (FMF) attacks, as well as FMF-associated amyloidosis. Unfortunately, colchicine is neither always effective nor always well tolerated, leaving some patients and their physicians with inadequate weaponry to fight this hazardous disease. We present a patient with recurrent episodes of abdominal, scrotal, and joint attacks, who was diagnosed with FMF and advised to take colchicine. Diarrhea prevented optimal treatment with this drug and led to a trial of etanercept, with resolution of FMF manifestations. This case adds to a growing body of evidence suggesting that tumor necrosis factor (TNF) blockade may result in resolution and prevention of further FMF attacks.