The US Navy has a long history of responding to disasters around the globe. US Navy ships have unique characteristics and capabilities that determine their capacity for a disaster response. This paper discusses common considerations and lessons learned from three distinct disaster missions. The 2010 earthquake in Haiti had a robust response with multiple US Navy ship platforms. It was best assessed in three phases: an initial mass casualty response, a subacute response, and a humanitarian response. The 2017 response to Hurricane Maria had a significant focus on treating patients with acute needs secondary to chronic illnesses to decrease the burden on the local healthcare system. The COVID-19 response brought distinctive challenges as it was the first mission where hospital ships were utilized in an infectious disease deployment. The first ships to respond to a disaster will need to focus on triage and acute traumatic injury. After this first phase, the ship's medical assets will need to focus on providing care in a disrupted health care system which most often includes acute exacerbations of chronic disease. Surgeons must be ready to be flexible in their responsibilities, be competent with end-of-life care, and negotiate technical and cultural communication challenges.