Patients with right bundle branch block and J-point elevations are at risk of sudden death. In the setting of recurrent syncope, polymorphic ventricular tachycardias or aborted sudden death they are highly suspicious of Brugada syndrome. Pharmacological challenge with sodium channel blocking agents in order to unmask or accentuate changes in the right precordial leads towards a prominent J-point elevation is an important diagnostic maneuver. Systematic studies in patients with Brugada syndrome have demonstrated that a significant proportion of patients suffering from this SCN5A-gene mutation react with Brugada-like ECG changes on the administration of sodium channel blocking agents. It is yet unknown to what extent a negative result of pharmacological challenge makes the diagnosis unlikely or excludes the presence of a Brugada syndrome. The pharmacological challenge should be part of the diagnostic work-up in patients who suffer from recurrent cardiogenic syncope, polymorphic tachycardias or aborted sudden death in the absence of structural heart disease and in asymptomatic patients with right bundle branch block and J-point elevations.