Hypertrophic cardiomyopathy (HCM) largely remains an orphan disease. In the near future, however, novel, evidence-based translational approaches are likely to revolutionize its management via the development of agents targeting disease-specific substrates. In current clinical practice, appropriate use of the available pharmacological armamentarium may provide sufficient control of most common clinical manifestations and complications, allowing normal longevity in many HCM patients. As the burden of disease is often considerable, specific experience is required for decision-making and choice of the most appropriate regimens. The mainstay of treatment includes beta blockers and disopyramide for patients with obstructive HCM, and beta blockers and verapamil or diltiazem in non-obstructive disease. Sotalol and amiodarone are the drugs of choice for control of supraventricular and ventricular arrhythmias. Oral anticoagulants should be prescribed in all HCM patients with atrial fibrillation. In the subset of patients experiencing congestive symptoms associated with severe disease progression and systolic dysfunction, standard heart failure treatment is warranted including renin–angiotensin–aldosterone inhibitors and diuretics. Serial assessment and early identification of disease progression is key for timely implementation of appropriate treatment, keeping in mind that severe heart failure often occurs in the absence of overt systolic dysfunction. Novel approaches currently under scrutiny for HCM include myocardial metabolic modulation, late sodium current inhibition, and allosteric myosin inhibition.