The prevalence of back pain continues in spite of the many treatments available, without any single treatment emerging as a panacea. In routine practice, clinical examinations have tended to become more cursory, the result of increasing demands on clinicians’ time and possible 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. The purpose of this discussion is to assist the clinician in the development of a more specific problem-focused examination that can enhance the differential diagnosis of specific pain generators and lead to more patient-specific treatment. Attention is given to considering all aspects of the examination, including physical assessment as well as imaging studies, plus the clinicians’ ability to recognize pathologies seen on imaging studies as clinically significant or not. The importance of considering how failed treatments influence the differential diagnosis is also discussed.