Left ventricular hypertrophy (LVH) is prevalent in clinical practice; it is associated with increased risk of heart failure, diastolic dysfunction, arrhythmias, and sudden cardiac death. Typical LVH is defined as the thickening of interventricular wall and/or septum in non-invasive imaging. Microscopically, the sizes of cardiomyocytes of LVH region are enlarged, accompanied by the augmentation of protein synthesis, sarcomeric structural disarray, and apoptosis. Molecular mechanisms of the initiation and progression of LVH downstream of pathological stimuli have been of intensive research for over half a century. Nevertheless, current pharmacological therapy resembles that for heart failure, including β adrenoreceptor -blockers, Ca antagonists, diuretics, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, metabolic therapies, β3 AR-agonist, mitochondrial ROS degenerating compounds, or agents regulate protein homeostasis. It is timely to develop a new strategy for specific and effective treatment of LVH.