Neonatal abstinence syndrome (NAS) is reaching epidemic proportions related to perinatal use of opioids. There are many approaches to assess and manage NAS, including one we have outlined. A standardized approach is likely to reduce length of stay and variability in practice. Circumcision is a frequent, painful procedure performed in the neonatal period. The rationale for providing analgesia is presented as well as a review of methods. Pharmacogenomics and pharmacogenetics have expanded our understanding of diseases and their drug therapy. Some applications of pharmacogenomics to the neonatal period are presented, along with pediatric challenges of developmental expression of drug-metabolizing enzymes.