The polarographic reduction behavior of Pralidoxime (PRL) and Obidoxime (OBD) at a Hanging Mercury Drop Electrode (HMDE) was exploited for their determination in different samples. Based on the obtained differential pulse polarograms, standard addition method was used to determine these drugs in pharmaceutical formulations and biological fluid samples. Linearity in the peak currents was achieved in the concentration ranges of 5.4 x 10-8 to 4.0 x 10-5 M and 2.8×10-8 to1.4×10-5 M for OBD and PRL respectively.The detection Limit was found to be 2.5 x 10-8 M (PRL) and 1.8×10-8 M (OBD) with correlation coefficients of 0.9980 (PRL) and 0.9965 (OBD). The repeatability and reproducibility of the method were checked by recovery studies.