<p>The neural and cardiovascular systems are pivotal in regulating human physiological, cognitive and emotional states, constantly interacting through anatomical and functional connections referred to as the brain–heart axis. When this axis is dysfunctional, neurological conditions can lead to cardiovascular disorders and, conversely, cardiovascular dysfunction can substantially affect brain health. However, the mechanisms and fundamental physiological components of the brain–heart axis remain largely unknown. In this Review, we elucidate these components and identify three primary pathways: neural, mechanical and biochemical. The neural pathway involves the interaction between the autonomic nervous system and the central autonomic network in the brain. The mechanical pathway involves mechanoreceptors, particularly those expressing mechanosensitive Piezo protein channels, which relay crucial information about blood pressure through peripheral and cerebrovascular connections. The biochemical pathway comprises many endogenous compounds that are important mediators of neural and cardiovascular function. This multisystem perspective calls for the development of integrative approaches, leading to new clinical specialties in neurocardiology.</p>