Primary and emergency care physicians regularly confront left upper quadrant (LUQ) pain, which presents a diagnostic challenge necessitating a nuanced approach. This chapter caters to healthcare providers who evaluate patients with LUQ symptomatology, offering a practical guide for LUQ pain assessment. It underscores the significance of understanding LUQ anatomical structures and their vascular supply. Symptoms warranting surgical consultation, including acute or chronic abdominal pain, are highlighted. Conditions associated with the gastrointestinal tract, such as perforated peptic ulcer, small bowel obstruction, and splenic flexure colonic ischemia, are being discussed in this chapter. Moreover, splenic conditions, including rupture, abscess, and arterial aneurysm, are also being addressed. With this chapter, we aim to empower primary and emergency care providers with succinct, actionable knowledge for effective LUQ pain management.