In patients battling cancer, many aspects of antimicrobial treatment become more complex, and standard antimicrobial regimens may be inadequate. Various pathophysiological changes in critically ill patients with cancer significantly affect the pharmacokinetics (PK) of antimicrobials. In an unacceptably high percentage of these patients, variability of relevant PK parameters results in inadequate antimicrobial drug exposure across all drug classes. The pathogen, with its susceptibility to an antibacterial agent (ie, pharmacodynamics [PD]), is a given; however, drug exposure (ie, PK) can be influenced by adjusting the dosage regimen. Dosage optimization strategies to improve the probability of attaining the PK/PD target and, thus, achieve clinical success are a key area of current translational research. An intensified focus on dosage regimens targeted at bacterial killing of both the fully susceptible bacterial population and resistant mutants may prevent emergence of resistance while also better meeting the needs of this substantial patient population.