Ventricular fibrillation (VF), in most instances, is sustained by multiple wavefronts. The most important prerequisites for development and maintenance of VF are inhomogeneity in activation and recovery and shortening of refractoriness. If drugs are to be effective in removing VF or facilitating its electrical removal, this should occur by alteration of these electrophysiologic mechanisms. Assessment of the antifibrillatory properties of many drugs has been compromised by at least two factors: 1) the questionable appropriateness of the model, and 2) the failure to distinguish between prevention of VF and removal, or facilitation of electrical removal, of VF. Most instances of VF encountered clinically are secondary to acute ischemia; therefore, the most applicable model is acute myocardial ischemia with spontaneous VF. In this setting little is known about the effectiveness of lidocaine (L) or procainamide (PA). While there is more information regarding the role of L in prevention of VF, and of both L and PA in elevating ventricular fibrillation threshold, there is a lack of data on the roles of either drug in removal of existing VF. Thus we are left to speculate on the actions of L and PA that may account for their usefulness in the treatment of VF. These actions are the basis for a projection of the role of L and PA in the treatment of VF. There is evidence in animal models of acute myocardial ischemia to support the use of at least lidocaine in VF.