Realizing the vast medical benefits of validated protocols, recommendations and practice guidelines requires acceptance and implementation by frontline care providers. Knowledge translation is the science of accelerating the transfer of knowledge to practice by understanding and creatively addressing the barriers that prevent adoption of new professional standards. In an attempt to improve patient care and reduce mortality, the Surviving Sepsis Campaign and The Institute for Healthcare Improvement created the resuscitation and management bundles for patients with severe sepsis and septic shock. These bundles have been accepted as best practice by many clinicians since multiple clinical trials have produced similar positive results when they were implemented. However, transferring these research outcomes-based guidelines to the clinical practice arena has been associated with poor compliance due to important barriers to implementation. Delays in the adoption of sepsis bundles are not surprising since the time from validation to implementation of a new clinical practice is typically 17 years. Using sepsis bundles as a model, this article explores why guidelines are important, examines physician adherence to protocols, and reviews the literature on strategies to improve clinical compliance and enhance knowledge translation.