Earthquakes cause devastating effects, resulting in the deaths of thousands of people each year. Understanding the full range of impacts, including fatalities, and the pathophysiological mechanisms underlying these effects is crucial for mitigating the aftermath of earthquakes. Therefore, this review aims to: delineate the critical golden time periods following earthquakes and identify the most effective responses and resilience factors during these periods; accurately define the terminology for injuries sustained post-earthquake; elucidate the basic pathophysiology of CRUSH injury-induced myopathy, one of the most significant pathologies in post-earthquake patient management; explore the role of nitric oxide (NO) mechanisms in crush injuries, which are believed to be fundamental to the “smiling death phenomenon” and represent the unseen part of the iceberg; and highlight the importance of the 3 main phenomena responsible for mortality—acidosis, coagulopathy, and hypothermia—during disasters. This comprehensive review, based on the latest literature, encompasses search and rescue, pre-hospital processes, emergency department procedures, and subsequent internal and surgical management algorithms.