Topical local anesthetics in one form or another have been used for the past 20 years to alleviate the skin pain associated with needle puncture and venous cannulation in children. Although the application of topical anesthetic creams is painless compared with traditional local anesthetic infiltration of the skin and subcutaneous tissues prior to venipuncture and minor skin procedures, they remain underutilized, primarily due to their slow analgesic onset and inconsistent effectiveness. For a topical local anesthetic to be of practical use in busy clinical settings, it must be easy to apply, have minimal side effects, not require cumbersome equipment and be reasonably cost effective. Until recently, limitations in one or all of these areas have dissuaded pediatric practitioners from their routine use. However, recent advances in transdermal delivery technologies, have led to the emergence of a number of new delivery approaches that accelerate the onset time to 20 min or less and provide more consistent and deeper sensory skin analgesia. Although still in the early stages of investigation, technologies that promote the flux of drugs of all sizes through the skin by creating transient microchannels show great promise in circumventing the skin barrier and promoting the transdermal delivery of not only local anesthetics but also other drugs. Ultimately, the rationale to change clinical practice and use a new transdermal delivery system will depend upon the cost, ease of use, frequency of adverse events and the benefits to the patient relative to an alternative method.