The intestines are the primary site for nutrient, fluid and electrolyte absorption and secretion. Fluid and salt secretion in the colon are managed by a fine balanced system of transporting mechanisms. CFTR and NKCC-1 are two cell transporters, which have been identified as key players for fluid and electrolyte transportation across the cells’ membranes. During transcellular movement of ions, a mechanism must be in place to prevent shifts in cell volume. The antiporter NHE1 is involved in volume control but its regulator was unknown, so far. The author Thilo Schenck reports how he and his team caused a rapid change in cell volume of colonic crypt cells by exposing them to an osmotic shock and how the resulting transmembranous movements of electrolytes were studied by high speed video imaging. By specifically modulating intracellular AMP Kinase and the cell transporters NHE1 and CFTR, their fine-tuned interaction in cell volume regulation was revealed. This book describes the role of AMP Kinase acting as a volume sensor, which regulates CFTR and NHE1 activity to maintain a constant cell volume. The author concludes that AMP Kinase is the upstream regulator of NHE1.