Antibiotic resistance in conjunction with the erosion of the drug development pipeline may lead us into a bleak future, a “post-antibiotic era.” Because of a shortage of studies addressing treatment options for multidrug-resistant Gram-negative (MDRGN) infections in children, data must be extrapolated from the adult literature. However, even adult studies are limited by significant methodological flaws. We are in urgent need of pediatric specific pharmacokinetic/pharmacodynamic data for agents with activity against MDRGN infections as well as improved clinical outcomes studies. For the time being, we must rely on in vitro studies, observational data, and clinical experience to guide our therapeutic decisions. In this review, we discuss treatment considerations for infections caused by extended-spectrum β-lactamase–producing organisms, AmpC β-lactamase–producing organisms, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii in the pediatric population.