Hypertension is a common condition in chronic kidney disease and contributes to its progression. In this chapter, we provide a comprehensive overview of some of the multiple processes that participate in the pathogenesis of hypertension and its associated kidney end-organ damage. In particular, we started focusing on endothelial dysfunction, which is due to reduced production or bioavailability of nitric oxide, or an imbalance between endothelium-derived relaxing and contracting factors, the latter including angiotensin II and endothelin-1. Then, we discussed accumulating evidence pointing to innate and adaptive immune cells as key mediators in the initiation and progression of hypertension and its attendant kidney damage, delving into mechanistic insights from rodent and human studies. Finally, we described the clinical overlap and differences between malignant hypertension-associated thrombotic microangiopathy and atypical hemolytic uremic syndrome, with complement gene screening providing, in some cases, useful clues to distinguish the two disease entities.