The clinical diagnosis of acute appendicitis is challenging as patients present with an array of objective and subjective symptoms early or late in the disease course. Ultrasound is routinely performed in all patients with suspected acute appendicitis. Equivocal test results frequently require further assessments using other imaging techniques that are limited in scope during pregnancy because of issues involving safety, availability, and accessibility. Physical examination diagnostic signs in acute appendicitis during pregnancy have not been well studied. Studies failed to describe, standardize, or correlate the technique used to the pathologic disease process. Therefore, gaps remain in current knowledge regarding the usefulness and application of these tests during the physical examination. Improvement in diagnostic acumen is critically important, particularly in cases where there remains diagnostic uncertainty because of equivocal imaging results. This article reviews signs used to diagnose patients with acute appendicitis using a pathophysiologic approach based on visceral and cerebrospinal nerve pathways to explain the mechanism for a positive test result. It also suggests a framework to study them further to better understand their role, if any, in clinical practice.