Intensive care unit (ICU) patients present several unusual pharmacokinetic (PK) characteristics compared with less seriously ill patients, including increased distribution volume and variable clearance. Interpatient PK variability is often considerable and can produce a wide range of values for PK parameters and major differences in drug exposure. These analyses have led to the development of simulation techniques and population PK models to assess dosing regimens in specific patient subsets. Plasma concentrations may frequently overestimate target-site concentrations and therefore clinical efficacy. The unbound drug concentration at the infection site should be preferred. Although renal replacement therapy techniques are commonly used in ICU patients, data concerning antibiotic dosing in this setting remain limited. Administration of antibacterial agents by continuous infusion is becoming a common technique to avoid undesirable high peak concentrations and low trough concentrations and to optimize PK-pharmacodynamic indices.