Painful procedures in the neonatal intensive care unit are common, undertreated, and lead to adverse consequences. A stepwise approach to treatment should include pain recognition, assessment, and treatment, starting with nonpharmacologic and progressing to pharmacologic methods for increasing pain. The most common nonpharmacologic techniques include nonnutritive sucking with and without sucrose, kangaroo care, swaddling, and massage therapy. Drugs used to treat neonatal pain include the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen, and local and topical anesthetics. The indications, advantages, and disadvantages of the commonly used analgesic drugs are discussed. Guidance and references for drugs and dosing for specific neonatal procedures are provided.