Hypertrophic obstructive cardiomyopathy is the most common genetic cardiac disease and is generally characterised by asymmetric septal hypertrophy and intraventricular obstruction. Patients with severe obstruction and significant symptoms that persist despite optimal medical treatment are candidates for an invasive septal reduction therapy. Twenty years after its introduction, percutaneous transluminal alcohol septal ablation has been increasingly preferred for septal reduction in patients with drug refractory hypertrophic obstructive cardiomyopathy. Myocardial contrast echocardiography and injection of reduced alcohol volumes have increased safety, while efficacy is comparable to the surgical alternative, septal myectomy, which has for decades been regarded as the 'gold standard' treatment. Data on medium- and long-term survival show improved prognosis with survival being similar to the general population. Current guidelines have supported its use by experienced operators in centres specialised in the treatment of patients with hypertrophic obstructive cardiomyopathy.