Many pathologies can produce a symptomatic headache by disturbing the pain-sensitive structures of the brain. Headaches that mirror the natural history of these pathologies in severity and timing are classified as “secondary.” Identifying the affiliated condition causing the secondary headache can be a clinical challenge for providers across a range of specialties. Use of screening tools during a patient evaluation may help direct the provider’s attention to meaningful findings that suggest a secondary cause. Brain and vessel imaging with CT and MR technologies is incorporated into most secondary evaluations. Lumbar puncture, serum evaluations, catheter angiography, and other tools are useful as well. In this chapter, we seek to summarize the defining features of secondary headaches, address a clinical strategy for identifying those features in coordination with an appropriate diagnostic work-up, and complement that discussion with a review of the pathophysiology at the foundation of common “red flag” symptoms.