Indomethacin is a prostaglandin synthetase inhibitor sometimes used for tocolysis. Several placebo-controlled trials and trials comparing indomethacin to other potential first-line tocolytic agents support its efficacy for delaying delivery for >48 hours. Recent observational studies, however, have raised concerns about the safety of indomethacin, implicating it with increased rates of intraventricular hemorrhage and necrotizing enterocolitis. Careful analysis of these observational studies suggests that these results should be viewed with caution, because of uncontrolled confounding by indication. A recent decision analysis supports the risk/benefit analysis of indomethacin in this setting. Still, the future of indomethacin in preterm labor should be guided by well-designed prospective clinical trials. Such studies are underway.