Traditional analytical approaches of HPLC found to be insufficient for solving upcoming challenges in species specificity and sensitivity analysis. Modern analytical hybrid techniques which are referred as hyphenations have been introduced from the traditional techniques to overcome the challenges in the analysis of components. Hyphenated approaches combine separation and detection procedures through the use of chromatographic and spectroscopic techniques. The various hyphenations of that are developed until now are LC-MS, LC-NMR, LC-IR, LC-DAD and it also includes multi hyphenations like LC-MS-MS, LC-ESI-MS. These techniques show high specificity and sensitivity. Now-a-days various types of LC-MS systems with various types of interfaces are a commercially available. The application of these hyphenations in many sectors such as forensic science, environment, biotechnology, pharmaceutical field is discussed.