Identified over a decade ago, the With‐No‐Lysine[K] (WNK)s have been the subsequent focus of intense research into the renal handling of Na+, Cl‐, K+ and several rare monogenetic diseases. However the potential extra‐renal roles for WNKs have been less well explored. Thiazides and Gordon syndrome are known to have effects on bone mineral density, Ca2+ and PO43‐ homeostasis, which were originally assumed to be an indirect effect through the kidney. However, current data suggests a complex and direct role for WNKs in the physiology of bone. The WNKs also modulate systemic blood pressure at several levels including the vascular resistance vessels where they cause vasoconstriction by altering the abundance of the transient receptor potential canonical channel (TRPC) 3 and/or phosphorylation of the Na+‐K+‐2Cl‐ cotransporter (NKCC1) in vascular smooth muscle (VSM) cells. The WNKs and many of the cation‐coupled Cl‐ cotransporters they regulate are highly expressed in the central nervous system and recent work has suggested that WNK dysfunction may have a role in the development of autism, schizophrenia and hereditary sensory and autonomic neuropathy type 2 (HSAN2). Finally, the WNK‐Sterile 20 kinase (STE20) signalling axis represents an evolutionarily ancient mechanism for maintaining osmotic homeostasis but a rapidly expanding body of evidence also shows a role in immunity and cellular regulation. This article is protected by copyright. All rights reserved.