The electroneutral cation/Cl^- cotransporter family (SLC12A) is composed by two branches: the K-driven branch, composed of four members (KCC1, KCC2, KCC3, and KCC4), and the Na-driven branch, composed of three members (NCC, NKCC1, and NKCC2). K-Cl cotransporters mediate Cl^- efflux, are inhibited by phosphorylation, and are activated by dephosphorylation. Na-(K)-Cl cotransporters mediate Cl^- influx and are activated by phosphorylation. These cotransporters are mutated in human disease, are targets of diuretics and are collectively involved in the regulation of cell volume, neuronal excitability, and blood pressure. A single kinase/phosphatase pathway is thought to coordinate the activities of these cotransporters; however, the mechanisms involved are as yet unknown. The WNK kinases are emerging as key regulatory proteins for the SLC12A family. Mutations in WNK1 and WNK4 cause pseudohypoaldosteronism type II (PHAII), a Mendelian disease that features hypertension and hyperkalemia. WNK4 is a regulator of NCC and NKCC1; some of these effects are kinase-dependent, whereas others are independent. Furthermore, WNK1 modulates the effect of WNK4 on NCC. WNK1 has also been found to activate the protein kinases SPAK or OSR1, which regulate activation of various epithelial ion channels including de SLC12A family. WNK3 is coexpressed in different tissues with several cation/Cl^- cotransporters and regulates their activity. These data suggests WNKs are crucial components of the kinase/phosphatase signaling pathway that coordinately regulates the Cl^- influx and efflux branches of the SLC12A cotransporter family and so their activities. An overview of the WNK kinases effects upon all members of SLC12 family of cotransporters will be discussed.