Antibiotics are among the medications most frequently administered to the critically ill, a population with high levels of intra- and inter-individual pharmacokinetic variability. Our knowledge of the relationships among antibiotic dosing, exposure and clinical effect in this population has increased in recent decades. Therapeutic drug monitoring (TDM) of serum antibiotic concentrations is the most practical means of assessing adequate antibiotic exposure, though until recently, it has been underutilised for this end. Now TDM is becoming more widespread, particularly for the beta-lactam antibiotics, a class historically thought to have a wide therapeutic range. We review the basic requirements, indications, and targets for effective TDM of the glycopeptides, aminoglycosides, quinolones and beta-lactam antibiotics in the adult intensive-care setting, with a special focus on TDM of the beta-lactam antibiotics, the most widely used antibiotic class.