Treatment-resistant hypertension (TRH) is an increasingly common and clinically challenging hypertension phenotype associated with adverse impact on cardiovascular events and death. Recent evidence, although limited, suggests that TRH may also adversely affect health-related quality of life (HrQoL) and other patient-reported outcomes. However, the precise mechanisms for this link remain unknown. A number of recent studies focusing on both the general hypertensive population and those with TRH suggest that patient awareness of difficult-to-control blood pressure, chronically elevated blood pressure levels, and the use of aggressive medication regimens with attendant cumulative adverse effects may play significant roles. This review summarizes the existing literature on HrQoL in persons with TRH, highlights literature from the general hypertensive population with relevance to TRH, and discusses important remaining questions regarding HrQoL in persons with TRH.