Definitive evidence to settle the important clinical controversies we debated in this Journal Conference are not yet available. More randomized controlled trials are clearly needed for all of the topics presented. Additionally, neonatal and pediatric data are clearly lacking on most of these questions. The key points in many of the conversations on these controversial topics focused on the balance between efficacy and safety. When safety data exist without efficacy data, the uncontrolled variables often become the knowledge, experience, and support available in an individual intensive care unit. "New" therapies have the potential to help many patients but also have the potential to do great harm if clinicians do not follow standard guidelines and/or do not have the knowledge to use the therapy appropriately. It is clear that some current standards of care will be overthrown by future data while others will be finally substantiated. This Journal Conference queried the status quo to better enable clinicians to make informed decisions in the care of their critically ill patients.