Donepezil hydrochloride (DNP) is used for the treatment of mild to moderate dementia of the Alzheimer's type. The voltammetric behavior of DNP was studied at a glassy carbon electrode using cyclic, linear sweep, differential pulse (DPV) and square-wave (OSWV) voltammetric techniques. DNP exhibited irreversible anodic waves within the pH range 1.80 and 9.00 in different supporting electrolytes. The peak was characterized as being irreversible and diffusion-controlled. The possible mechanism of the oxidation process is discussed. The current-concentration plot was rectilinear over the range from 1 × 10-6 to 1 × 10-4 M in Britton-Robinson buffer at pH 7.0 with a correlation coefficient between 0.997 and 0.999 in supporting electrolyte and human serum samples using the DPV and SWV techniques. The repeatability and reproducibility of the methods for both media (supporting electrolyte and serum sample) were determined. Precision and accuracy of the developed methods were demonstrated by recovery studies. The standard addition method was used for the recovery studies. No electroactive interferences were found in biological fluids from endogenous substances or additives present in tablets. The methods developed were successfully applied to the determination of DNP in tablets and in spiked human serum.