Antipseudomonal carbapenems have played a useful role in our antimicrobial armamentarium for 20 years. However, a review of their use during that period creates concern that their clinical effectiveness is critically dependent on attainment of an appropriate dosing range. Unfortunately, adequate carbapenem dosing is missed for many reasons, including benefit/risk misconceptions, a narrow therapeutic window for imipenem and meropenem (due to an increased rate of seizures at higher doses), increasingly resistant pathogens requiring higher doses than are typically given, and cost containment issues that may limit their use. To improve the use of carbapenems, several initiatives should be considered: increase awareness about appropriate treatment with carbapenems across hospital departments; determine optimal dosing regimens for settings where multidrug resistant organisms are more likely encountered; use of, or combination with, an alternative antimicrobial agent having more favorable pharmacokinetic, pharmacodynamic, or adverse event profile; and administer a newer carbapenem with lower propensity for resistance development (for example, reduced expression of efflux pumps or greater stability against carbapenemases).