Differential Electrolytic Potentiometry has been applied successfully as a detector for Sequential Injection Analysis combined with flow injection system, this method was utilized in different types of ion-combination and charge transfer reactions. The developed methods was used for the determination of cyanide in real water samples using two silver amalgam electrodes, with high selectivity and the method was compared with the standard methods. Cyanide was also determined by sequential injection analysis method using spectrophotometric detection. The DEP detection system was applied for sequential injection determination of Lansoprazole, Pantoprazole, Procainamide hydrochloride and ascorbic acid using platinum working electrodes, the method was applied for real samples and it was compared with the standard methods. For all the studied systems the variables that affect the signals were investigated using the univariate method of optimization, those variables include reagent solution concentration, flow rate, volumes, current density and delay time. The developed methods are rapid, simple, less costly and precise compared to other methods. Cinoxacin antibiotic was determined using simple titrimetric method based on DEP detection, using antimony electrodes. Lansoprazole and Pantoprazole were also determined using kinetic spectrophotometric method based by their oxidation reaction with Potassium permanganate. For the first time DEP was coupled with HPLC as a potential detector and it was applied for the determination of Ascorbic acid in real samples successfully.