Recent development in the pharmaceutical applications of polyion sensitive electrodes (PSEs) is reviewed. The general electrochemical principle governing the potentiometric response of such polymer membrane based devices is summarized and applications for the use of these novel sensors are detailed. These new applications include methods to quantitate the anticoagulant heparin and pentosan polysulfate, an anti-osteoarthritis drug, via titration with polycationic protamine or polyarginine, as well as selective assay on fibrinolytic enzymes (e.g., plasminogen activators and plasminogen) using protamine as the substrate based on potentiometric polyion detection.