While a large number of studies has examined the efficacy of opioid-sparing analgesics in adult surgical populations, fewer studies are available to guide postoperative pain treatment in pediatric patients. We systematically reviewed available publications on the use of systemic nonopioid agents for postoperative analgesia in pediatric surgical populations. A comprehensive literature search identified meta-analyses and randomized controlled trials (RCTs) assessing the effects of systemic, nonopioid agents on postoperative narcotic requirements or pain scores in pediatric surgical populations. If a meta-analysis was located, we summarized its results and any RCTs published after it. We located and reviewed 11 acetaminophen RCTs, 1 nonsteroidal anti-inflammatory drug (NSAID) meta-analysis, 2 NSAID RCTs, 1 dexamethasone meta-analysis, 3 dexamethasone RCTs, 2 ketamine meta-analyses, 5 ketamine RCTs, 2 gabapentin RCTs, 1 clonidine meta-analysis, 3 magnesium RCTs, 2 dexmedetomidine meta-analyses, and 1 dextromethorphan RCT. No meta-analyses or RCTs were found assessing the perioperative efficacy of intravenous lidocaine, amantadine, pregabalin, esmolol, or caffeine in pediatric surgical patients. The available evidence is limited, but suggests that perioperative acetaminophen, NSAIDs, dexamethasone, ketamine, clonidine, and dexmedetomidine may decrease postoperative pain and opioid consumption in some pediatric surgical populations. Not enough, or no, data exist from which to draw conclusions on the perioperative use of gabapentin, magnesium, dextromethorphan, lidocaine, amantadine, pregabalin, esmolol, and caffeine in pediatric surgical patients. Further pharmacokinetic and pharmacodynamics studies to establish both the clinical benefit and efficacy of nonopioid analgesia in pediatric populations are needed.