The North American beef cattle industry has endured many changes throughout the years but is encountering some of the most dramatic challenges in history during the first decade of the 21st century. The US beef cattle inventory increased from 1990 to a high of 103.5 million in 1996 and since has declined to a low of 94.5 million on 1 January 2009. Even though economic signals have encouraged the cow herd to increase over the last 5 years, a significant decrease occurred during 2008. It is difficult to determine the precise cost of bovine respiratory disease (BRD) to the industry but it is reported to be greater than US$500 million per year. Data from our practice indicate that losses from BRD over the last 18 years have been characterized by 5-year cycles of decreases and increases. Perhaps it is time for the industry to look for ways to reduce death loss by methods that focus on the animal's response to the pathogens instead of continuing to focus on the pathogens.