Indomethacin, a nonspecific prostaglandin synthetase inhibitor, gained popularity several decades ago as a potent tocolytic agent. This popularity, however, was tempered by concerns over fetal and neonatal complications associated with its use. However, with better recognition of the safety limitations, there has been a renewed interest in using indomethacin for acute tocolysis. More recently, the tocolytic potential of cyclooxygenase-2 (COX-2) specific inhibitors has gained much interest as well as the theoretical minimization of side effects associated with these agents. This article reviews the pharmacology and efficacy of indomethacin and some of the newer cyclooxygenase-2 inhibitors, and discusses the potential adverse fetal and neonatal effects associated with their use. Guidelines will be presented that will assist theclinician in using indomethacin as an effective tocolytic while avoiding untoward effects.