Noninvasive ventilation (NIV) has gained increased acceptance inside the critical area, since it has been shown to be effective in reducing or avoiding the need for oro-tracheal intubation. NIV efficacy is dependent on the selection of the appropriate patients and on their compliance to therapy. Actually, full collaboration is not easily reached especially in agitated patients.Sedation during NIV is useful to reduce the rate of treatment failure, but robust data to guide the development of best practice are limited and sometimes local customs appear to exert a strong influence on patterns of care. Different sedative drugs are ready for use but none of currently available agents fulfill the criteria for the ideal drug. Knowledge of the pharmacological and hemodynamic characteristics of every single sedative agent is crucial to choose the right drug for every clinical scenario. Close monitoring is mandatory to avoid adverse effects. The aim of this article is to review the currently available literature, to recognize the contraindications for sedation use and to provide practical guidance.