Introduction - Epilepsy is a disease characterized by the occurrence of spontaneous seizures of various shapes, and these seizures are due to an outbreak of neuronal electrical episodes. Modern antiepileptics are effective in controlling the seizures, but their using is limited by side effects. Because patients consume these drugs regularly over years, it's important to have as few side effects. Lamotrigine is a drug that belongs to the "newer" antiepileptics which certainly has become one of the important drugs and the treatment of epilepsy it's impossible without it today. Today, the serum concentrations of lamotrigine are routinely determined to check if the patient takes a regular treatment or when the dose of the drug is changed. Aim – To show the advantages of using HPLC method, liquid chromatography with UV detection at a quantitative determination of the concentration of lamotrigine in patients on daily treatment with this medicine. Methods - Liquid chromatography with UV detection, HPLC-UV is the most commonly used method for determining the concentration of the new generation of antiepileptic drugs, lamotrigine. Samples were prepared by extraction of the solid carriers, SPE in alkaline solution with the addition of sodium hydroxide solution and then injected to HPLC analysis instrument. Lamotrigine was detected at a wavelength of 306 nm and a flow rate of 2 mL / min. Results – In this study, samples of patients that contained a certain amount of lamotrigine, are being analyzed. The samples were passed through the column at at a flow rate of 2mL/min and at a wavelength of 306 nm. It was the high wavelength avoided interference which may be present in the sample. We obtained the best chromatography response at pH of 6.9. Conclusion – Following the analysis it can be concluded that the HPLC-UV method is sufficiently sensitive and accurate for the determination of serum concentrations of lamotrigine in patients. The advantage of this method is quicker sample preparation and short time duration of analysis with reliable results which is especially important in emergencies.