The randomized controlled trial (RCT) has become the “gold” standard for clinical research. However, the complex nature of critical illness has made the design and conduct of RCTs difficult. Research in critically ill patients presents unique challenges. The disease processes are often not well defined. There are also multiple therapeutic interventions being administered and the disease processes themselves often have a variable clinical course. Finally, outcome selection is a challenge, mortality (short or long) versus nonmortality outcomes. The last few years have seen the publication of the results of five RCTs that have had a major impact on the practice of critical care.