Our body is continuously in contact with external stimuli that need a fine integration with the internal milieu in order to maintain the homeostasis. Similarly, perturbations of the internal environment are responsible for the alterations of the physiological mechanisms regulating our main functions. The nervous system and the immune system represent the main interfaces between the internal and the external environment. In carrying out these functions, they share many similarities, being able to recognize, integrate and organize responses to a wide variety of stimuli, with the final aim to re-establish the homeostasis. The autonomic nervous system, which collectively refers to the ensemble of afferent and efferent neurons that wire the central nervous system with visceral effectors throughout the body, is the prototype system controlling the homeostasis through reflex arches. On the other hand, immune cells continuously patrol our body against external enemies and internal perturbations, organizing acute responses and forming memory for future encounters. Interesting to notice, the integration of the two systems provides a further unique opportunity for fine tuning of our body's homeostasis. In fact, the autonomic nervous system guides the development of lymphoid and myeloid organs, as well as the deployment of immune cells toward peripheral tissues where they can affect and control several physiological functions. In turn, every specific immune cell type can contribute to regulate neural circuits involved in cardiovascular function, metabolism, inflammation. Here we review current understanding of the cross-regulation between these systems in cardiovascular diseases.