Nephrogenic systemic fibrosis (NSF) is a recently described systemic fibrosing disorder that develops in the setting of renal insufficiency. Exposure to gadolinium has been implicated in its development. While the primary manifestations are cutaneous, systemic fibrosis can also occur. Several anecdotal reports of successful treatment have been reported, but there is no consistently efficacious therapy. We report the improvement or stabilization of cutaneous disease in three patients with NSF using alefacept therapy.