In this chapter we discuss sepsis-induced inflammation and organ dysfunction, as well as the role of autophagy as a protective cell signaling mechanism. Sepsis is a leading cause of death worldwide, and is the most common precipitant of organ dysfunction. It has been noted that a minimal amount of cell death is present in patients who succumb to sepsis-induced organ failure and that, after the septic insult has passed, organs have the potential to regain function, suggesting a hibernating state of the cell in order to protect it from apoptosis and death. The cellular and molecular processes involved in sepsis are complex, and continue to be elucidated. Autophagy has been extensively studied in recent decades and an exponential increase in knowledge regarding this physiological pathway used by cells has been found. It is known to be activated under stress conditions in order to protect the cell from dying. In the setting of sepsis it has been demonstrated to play an important role for recycling of unhealthy mitochondria and damaged organelles, thus decreasing injury by ROS and providing nutrients and amino acids that the cell can use in this stressful environment. The purpose of this chapter is to review what is known about autophagy in sepsis and describe the contributing mechanisms by which autophagy can protect against organ injury.