Cross-talk is broadly defined as endogenous homeostatic signaling between vital organs such as the heart, kidneys and brain. Kidney-brain cross-talk remains an area with excitingly few publications despite its purported clinical relevance in the management of currently undertreated conditions such as resistant hypertension. Therefore, this review aims to establish an organ-specific definition for kidney-brain cross-talk and review the available and forthcoming literature on this topic. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.