A brief failure of one item on the display of the information system (IS) on Flight AF 447 wrought havoc in the coordination between the pilots and the aircraft, leading to the loss of all 228 lives on board. In this essay, we ask the following question: How can the very instruments supposed to ensure our safety and make organizations more reliable lead a team to destruction? We propose that the imbrication of material and human agencies in such highly automated systems drives an attitude of “mindful indifference” (i.e., the capacity for experienced operators to distinguish problems that could turn into critical ones from problems that can be tolerated on account of the overall system reliability). An abrupt change in this imbrication provoked emotional distress and focused the pilots’ attention toward the machine, instead of triggering an organizational process of sensemaking. We highlight the role of leadership in such situations.