Lithium salts are still one of the most popular therapeutic approaches to the treatment of bipolar disorders, notwithstanding the introduction of more modern, less toxic drugs. Because of a narrow therapeutic range, lithium serum concentrations must be strictly monitored during the treatment to avoid life-threatening neurotoxicity. For this purpose, methods based on flame photometry or ion-selective electrodes are usually applied. The aim of the present work was to develop and validate a simple method for the determination of lithium in serum based on capillary zone electrophoresis with indirect detection. A validation of the method was carried out, including a comparison with an automated routine method based on ion-selective electrodes.