A wide range of substances, including drugs and illicit compounds, increase the risk of epileptic seizures. In this systematic review, the authors address the issue of the epileptogenic potential of marketed drugs, with the aims of providing criteria for the assessment of the cause-effect relationship between drug exposure and the risk of seizures; and to identify the compounds better fulfilling the requirements of an epileptogenic drug. Finding a correlation between drug exposure and occurrence of seizures does not necessarily establish a causal association. In light of the available evidence, even with these limitations, some conclusive remarks can be made on the epileptogenic potential of some active principles. Drugs with high epileptogenic potential include meperidine, sevoflurane, clozapine, phenothiazines and cyclosporine. Drugs with intermediate epileptogenic potential include propofol, maprotiline, tricyclic antidepressants and chlorambucil. Drugs with low epileptogenic potential include fluorquinolones, carbapenems, bupropion and iodinated contrast media. Drugs with minimal or inconclusive epileptogenic potential include interferon alpha.