The number of diagnostic and therapeutic interventions performed under sedation is growing rapidly. While providing patients with an improved experience secondary to anxiolysis, analgesia, and amnesia, sedation also puts them at risk for associated cardiorespiratory and other complications. Several medications are available for sedation, all of which have unique advantages and disadvantages. The combination of patient characteristics, procedural factors, and side effects associated with each medication places each patient at risk and therefore, vigilance during sedation cannot be overemphasized. Due vigilance includes proper monitoring, training, staffing, and equipment, all of which are essential to the safe delivery of sedation.