Throughout history, numerous infectious diseases have emerged and re-emerged. Microbial adaptation and change, globalisation, increased migration, public health infrastructure, climate change and environmental degradation contribute to their emergence and re-emergence. In recent years, the Caribbean has experienced “two pandemics”, namely HIV/AIDS and COVID-19, and major outbreaks of dengue fever, chikungunya and zika viruses. These diseases and others lead to significant mortality, morbidity, social and economic losses and continue to challenge health and other sectors. In addition, while tuberculosis, malaria and influenza remain important the surge of other diseases in the region or nearby such as Mayaro virus disease and Oropouche virus disease, which are underreported, remains a cause for concern as they are linked to travel and tourism, can disrupt health systems, impact societies and devastate economies. Antimicrobial resistance (AMR) has been identified as one of the greatest challenges to public health, and addressing AMR requires the support of multiple actors taking a One Health approach. In this chapter, we discuss major emerging and re-emerging infectious diseases which have affected or continue to have significant impact in the context of the Caribbean.