A simple, specific and accurate RP-HPLC method was developed for the simultaneous analysis of Naltrexone hydrochloride (NTX) and Bupropion hydrochloride (BUP) in bulk and dosage forms. A Phenomenex C18 column (250 x 4.6mm; 5 μm) with mobile phase containing 0.05% v/v triethylamine (pH6.5): acetonitrile (45:55% v/v) was used at isocratic mode and eluents were monitored at 215 nm. The retention times of NTX and BUP were 3.4 min and 12.7 min respectively and showed a good linearity in the concentration range of 40-200 μg/mL of NTX and 10- 50 μg/mL of BUP with a correlation coefficient of 0.999 and 0.998 respectively. The average recoveries were found to be 98.60% and 98.90% respectively for NTX and BUP. The proposed method was validated as per ICH guidelines and successfully applied to the simultaneous estimation of NTX and BUP in bulk and dosage forms.