In order to review the epidemiology of Gram-negative infections in the pediatric and neonatal intensive care units (PICUs and NICUs) of Latin America a systematic search of PubMed and targeted search of SciELO was performed to identify relevant articles published since 2005. Independent cohort data indicated that overall infection rates were higher in Latin American PICUs and NICUs versus developed countries (range, 5%-37% vs 6%-15%, respectively). Approximately one third of Latin American patients with an acquired PICU or NICU infection died, and crude mortality was higher among extremely low-birth-weight infants and those with an infection caused by Gram-negative bacteria. In studies reporting > 100 isolates, the frequency of Gram-negative pathogens varied from 31% (Colombia) to 63% (Mexico), with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli the predominant pathogens in almost all countries, and Acinetobacter spp. and Serratia spp. isolated sporadically. The activity of quinolones and third-generation cephalosporins against P. aeruginosa, Acinetobacter spp., and Enterobacteria was seriously compromised, coincident with a high prevalence of circulating extended-spectrum β-lactamases. Furthermore, we identified two observational studies conducted in Chile and Brazil reporting infections by P. aeruginosa and Acinetobacter baumannii in PICUs, demonstrating resistance to carbapenems, and two outbreaks of carbapenem-resistant K. pneumoniae in Colombia and Brazil. The endemicity of multidrug-resistant Gram-negative infections in Latin American PICUs and NICUs is punctuated by intermittent clonal outbreaks. The problem may be alleviated by ensuring ICUs are less crowded, increasing staffing levels of better-trained health care personnel, and implementing antimicrobial stewardship and surveillance programs.