During the past two decades there has been a substantial increase in the number and types of topical anesthetics available. Options for the prevention of neonatal pain associated with skin-breaking procedures were previously limited to injections of lidocaine hydrochloride. Topical anesthetics are now available as creams, gels, and a heat-activated patch system. Although lidocaine injection continues to be widely used for pain associated with circumcision, lumbar puncture, or placement of central venous lines, practical information regarding the use of newer agents in the neonate is needed. This review seeks to expand the options for topical anesthesia in neonates.