Ensuring effective, safe drug dosing in critically ill patients can be difficult, due to variable and dynamic organ function. An 82-year-old man was admitted to the intensive care unit with severe community-acquired pneumonia, septic shock and progressive organ failure. He required ventilation and continuous renal replacement therapy. He developed seizures which we believe were due to cefepime toxicity. Following the first seizure, we took serial measurements of plasma cefepime levels, and a single measurement of the cerebrospinal fluid (CSF) cefepime level. The peak plasma cefepime concentration was 73.8 µg/mL (minimum inhibitory concentration of target enterobacteriaceae is 8 µg/mL) and the CSF level was 6.1 µg/mL. The patient had four seizures during the period of high plasma cefepime concentration, but no more episodes once the drug level decreased to non-toxic levels. This case highlights the difficulty in predicting pharmacokinetics in critically ill patients, particularly those receiving renal replacement therapy. We suggest that therapeutic drug monitoring in critically ill patients may be a useful intervention to avoid antibiotic-related toxicities.