Arterial hypertension remains a primary global health problem with significant impact on cardiovascular morbidity and mortality. The low rate of hypertension control and failure to achieve target blood pressure levels particularly among high-risk patients with resistant hypertension has triggered renewed interest in unravelling the underlying mechanisms to implement therapeutic approaches for better patient management. Here, we summarize the crucial role of neurogenic mechanisms in drug-resistant hypertension, with a specific focus on central control of blood pressure, the factors involved in central integration of afferent signalling to increase sympathetic drive in resistant hypertension, and briefly review recently introduced interventional strategies distinctively targeting sympathetic activation.