BACKGROUND: Since 2014, the number of migrants and refugees crossing the Mediterranean towards Europe has risen significantly due to various reasons. Both state agencies and non-governmental organizations (NGOs) have launched rescue missions in the Central Mediterranean in accordance with international legal obligations for search and rescue (SAR) operations for those under distress at sea. Our aim is to summarise the specific qualifications needed for maritime SAR in the Mediterranean both in terms of the population at risk, the equipment and the medical support required, especially during the coronavirus disease 2019 (COVID-19) pandemic and the operational legal framework. MATERIALS AND METHODS: This article aims to summarise the key points of SAR efforts from a medical perspective as depicted in the relevant literature during a specific timeline period (2014-2020) in a specific part of the Mediterranean Sea (Central Mediterranean route). Only papers published in English and whose full text was available were included in this study. The inclusion criteria were: a) articles referring to sea rescue operations between 2014 and 2020, b) research that focused on medical preparedness and assistance during rescue operations in the Central Mediterranean route, c) studies concerning demographic and clinical features of the rescue population, d) guidelines on the rule of conduct of persons and states participating in rescue activities. The exclusion criteria were: a) studies describing SAR operations in different regions of the world and b) studies focusing on routes, demographics and medical support of migrants/refugees on land. RESULTS: Three major themes were identified: a) characteristics of the population in distress at sea: country of origin, age groups, presence of communicable and non-communicable diseases were identified in the relevant literature. Our research shows that dermatological and respiratory issues were the major concerns among sea migrants, coming from different countries of both Africa and Asia, being relatively young and mostly males; b) medical preparedness and equipment needed for rescue: according to current guidelines, revised during the COVID-19 pandemic, infrastructure needed during SAR operations includes both equipment for resuscitation, personal protective equipment, deck adjustments, medical personnel trained to function in an austere setting and able to handle vulnerable patient groups such as children and pregnant women; c) medico-legal implications of SAR operations: knowledge of the legal framework encompassing SAR operations seems necessary, as European Union and state led initiatives seem to withdraw from proactive SAR, while criminalising NGO led rescue efforts. Operating with the imperative to save lives seems to be the only way of respecting international law and human values, thus, a summary of what the law dictates was made in an effort to keep medical workers participating in such operations updated. CONCLUSIONS: Investigation aims to shed light on the special clinical features of sea migrants, the skills, equipment and organizational structure needed by medical workers participating in SAR operations as well as the legal framework under which they will be asked to operate. Special consideration will be given to the difficulties that emerged due to the COVD-19 pandemic.