The development of an effective target for therapeutic intervention remains a critical part of the drug discovery process. One such target class is the P-type ion translocating ATPases, which include the Na+,K+-ATPase of cardiac cells and the H+,K+-ATPase of gastric parietal cells. These enzymes serve as selective targets for digoxin and omeprazole, which are used to treat heart disease and gastrointestinal ulcers, and are two of the leading prescribed therapeutics worldwide. It is the exquisite selectivity that can be achieved between family members that continues to make the P-type enzymes desirable targets for developing new therapeutics including a new generation of antiulcer therapeutic and a new class of antifungal therapeutic.