Patients with hypertrophic cardiomyopathy who experience refractory symptoms due to left ventricular outflow tract obstruction are often referred for definitive therapy consisting of either surgical myectomy or alcohol septal ablation (ASA). There currently exists clinical equipoise regarding which therapy is the most efficacious in this challenging patient population. ASA utilizes common interventional techniques usually employed to treat atherosclerotic coronary artery disease to inject small aliquots of ethanol into a branch of the appropriate septal vessel to cause necrosis of the obstructing basal septal tissue. Myocardial contrast echocardiography is used to facilitate location of the most appropriate septal branch with success determined by an acute reduction in the resting and/or provoked gradient. Recent comparative data have suggested similar rates of long and short-term mortality in when comparing patients undergoing ASA and surgical myectomy, with ASA patients experiencing a higher rate of requirement for permanent pacemakers. In addition, patients treated by both techniques appear to have similar gradient reductions and improvement in symptomatic status. Comparisons of these two methods of treatment are limited by the non-randomized nature of the studies, retrospective data collection and the allocation of higher-risk patients to ASA treatment. Concern for the wide-spread adoption of ASA to drug-resistant HCM patients is warranted due to the potential for arrhythmogenesis is a patient population already at risk for life-threatening arrhythmias. There have been case reports of such arrhythmias, however, clinical series to date have not suggested an enhanced risk of sudden cardiac death in patients treated with ASA. Definitive answers concerning which patient subsets with drug-refractory hypertrophic cardiomyopathy would benefit from the two competing therapies can only be answered by a randomized clinical trial. However, for a variety of clinical and logistical factors, such a trial is unlikely to ever be performed. For the foreseeable future, patient-specific therapy will depend on local expertise, patient comorbidities and preferences.