The majority of patients presenting to a primary care physician with acute chest pain will have non-life-threatening etiologies. Nevertheless, catastrophic cause of chest pain such as ACS, AD, PE, esophageal perforation, and pericarditis must be considered in the differential diagnosis. Often, these deadly conditions have atypical clinical presentations that must be recognized. Furthermore, the physical examination can be deceptively benign in patients harboring a catastrophic etiology of chest pain. By identifying these atypical presentations, recognizing the utility of the physical examination, and understanding of the limitations of traditional diagnostic imaging, primary care physicians can effectively diagnose patients who have life-threatening cause of acute chest pain.