The prevalence of back pain continues despite the many treatments available, without any single treatment being a panacea. In routine clinical practice, clinical examinations may be more cursory, influenced by increasing demands of time and an overreliance on technology. It has been suggested that the failure to adequately differentially diagnose the cause of back pain can account for clinical failures in treatment. This discussion will assist clinicians in the development of more specific problem focused examinations to enhance the differential diagnosis of specific pain generators and therefore lead to more patient centered specific treatments with the goal of enhancing clinical outcomes. Attention will be given to consideration of all examination aspect, including physical assessment as well as imaging studies, and the ability to rationalize when pathologies seen on imaging studies may or may not be clinically significant. The importance of considering how failed treatments influence the differential diagnosis will also be discussed.