This chapter provides a summary of the landmark study known as a protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. Can duration of mechanical ventilation be reduced with a protocol of no sedation versus daily interruption of sedation? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. Understanding that not all patients receiving mechanical ventilation require sedation is an important first step to determining the best regimen.