For clinicians, the implications are potentially significant. First, their data suggest that many critically ill patients have “augmented renal clearance (ARC).” Because of their underlying hyperdynamic states, treatment with vasopressors, and exposure to fluid resuscitation, it appears that a distinct cohort of patients in the ICU have supraphysiologic renal function. Reliance on a simple measurement of serum creatinine will miss this phenomenon. Second, and more important, the potential for ARC suggests that, for some patients, we are clearly using the incorrect dosages for antibiotics. We continue to presume that one set dose is the appropriate dose for all patients in the ICU, and this is clearly erroneous. This concept that “one dose fits all” derives from a failure to recognize clinical heterogeneity at the bedside and simultaneously permeates the conduct clinical trials for new antibiotics. Again, the case of ceftobiprole is illustrative. In the clinical trial of this antimicrobial for VAP, many subjects displayed ARC. Tied together with the poor penetration of ceftobiprole into the lung, many persons with VAP likely never achieved adequate drug levels in the lung to eradicate troublesome pathogens. Thus, it was not surprising that this molecule at the dose studied proved inferior to comparator.