This work is concerned with application of simple, economical, precise, accurate and reproducible reverse phase high performance liquid chromatographic (RP-HPLC) method for simultaneous estimation of Nebivolol hydrochloride(NBH) and S-Amlodipine besylate (AMB) on thermo Hypersil C18 (Thermo Electron Corporation) (250 x 4.6 mm, 5 μm) using Acetonitrile and Phosphate buffer (pH 2.5 ± 0.1) in ratio of 60:40 as mobile phase. pH of buffer adjusted to 2.5 ± 0.1 with O-phosphoric acid. The flow rate was adjusted at 1.0 ml/min and the detection wavelength was 271 nm. The retention time for AMB and NBH was found to be 6.39 and 7.54 min, respectively. Proposed method was validated for precision, accuracy, linearity range, robustness and ruggedness.