It is important for clinicians to understand, incorporate, and follow a logical and relevant order when assessing a patient’s presenting problem while keeping in mind that the utilization of clinical judgment is always a key deciding factor in patient care. This allows for a more educated and accurate conclusion when considering competing and differential diagnoses. This lecture will highlight pertinent red flags and presenting signs and symptoms that should; clue the practitioner into recognizing that a serious problem exists and help the practitioner discern any competing issues that need to be immediately addressed. We will elaborate on patient history, assessment, and presenting indicators and what signals the ordering of basic and advanced imaging, diagnostic studies, and/or pertinent referrals to other specialties. Visceral pain and neck, mid back, and lower back pain “zebras”, non-musculoskeletal issues, and general assessment and strategy will be discussed. There will be a brief overview of some common presenting musculoskeletal related conditions relevant to the spine.