Acute abdominal pain represents the cardinal symptom of a large number of intra-abdominal pathologies. Because of multiple organ systems, varied pathology from life threatening to benign, and differences in presentation related to sex and age, identifying a final diagnosis is a challenge. The clinician’s goal for patients with acute abdominal pain is to rapidly identify whether the underlying cause requires an urgent or immediate surgical intervention. By developing a systematic approach to evaluating patients with abdominal pain, clinicians can generate a differential diagnosis to ensure appropriate treatment and improved patient outcomes. The purpose of this article is to provide clinicians with a framework for evaluating the complaint of acute abdominal pain and recognizing patients who require expedited evaluation.