Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was investigated under forced thermal and hydration stress conditions as recommended by the International Conference on Harmonization guidelines. In addition, competency of vibrational(infrared and Raman) spectroscopy was assessed to identify structural changes of the drug symbolizing its stress degradation. High performance liquid chromatography was used as a confirmatory technique for both thermal and hydration stress study, while thermogravimetric analysis/differential thermal analysis and atomic force microscopy substantiated the implementation of vibrational spectroscopy in this framework. The results exhibited high thermal stability of the drug as significant variations were observed in the diffuse reflectance infrared Fourier transform spectra only after the drug exposure to thermal radiations at 100 °C. Hydration behavior of ritonavir sulfate was evaluated using Raman spectroscopy and the value of critical relative humidity was found to be 4 67%. An important aspect of this study was to utilize vibrational spectroscopic technique to address stability issues of pharmacological molecules, not only for their processing in pharmaceutical industry, but also for predicting their shelf lives and suitable storage conditions. Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was investigated under forced thermal and hydration stress conditions as recommended by the International Conference on Harmonization guidelines. In addition, competency of vibrational (infrared and Raman) spectroscopy was assessed to identify structural changes of the drug symbolizing its stress degradation. High performance liquid chromatography was used as a confirmatory technique for both thermal and hydration stress study, while thermogravimetric analysis / differential thermal analysis and atomic force microscopy substantiated the implementation exhibition vibrational spectroscopy in this framework. The results illustrated high thermal stability of the drug as significant variations were observed in the diffuse reflectance infrared Fourier transform spectra only after the drug exposur e to thermal radiations at 100 ° C. Hydration behavior of ritonavir sulfate was evaluated using Raman spectroscopy and the value of critical relative humidity was found to be 4 67%. An important aspect of this study was to utilize vibrational spectroscopic technique to address stability issues of pharmacological molecules, not only for their processing in pharmaceutical industry, but also for predicting their shelf lives and suitable storage conditions.