Numerous studies revealed that the effective rate of β-blockers for hypertension treatment is about 50∼60%, which was mainly due to interindividual difference in drug response, especially for β-blocker metoprolol. Previous studies have demonstrated that cytochrome P450 2D6 (CYP2D6) and β1-adrenergic receptor (ADRB1) gene polymorphisms could affect metoprolol antihypertensive efficacy. However, even for patients with essential hypertension who have the same genotype in CYP2D6 and ADRB1 genes, their response to metoprolol is still different. Recently, we found that antihypertensive effects of metoprolol would be improved by increasing the expression level of myocardial Adrb1 in spontaneously hypertensive rats which had the same genotype. Therefore, we present a hypothesis that the expression level of myocardial ADRB1 could affect the antihypertensive effects, which may be a novel mechanism for interindividual difference in patients with essential hypertension treated by metoprolol.