Infectious disease outbreaks either endemic or emerging and re-emerging infectious diseases contribute to the burden of infectious disease particularly in limited resource settings. The management of outbreaks is quite demanding given the number of cases and sometimes deaths that occur. The incidence of some disease outbreaks has risen over time and somewhat exacerbated by other emerging and re-emerging diseases of pandemic propensity. The COVID-19 pandemic challenged the already struggling health systems and affected routine public health programmes globally. There is need for endemic countries to review the successes and failures during the pandemic and identify gaps and areas that need strengthening to build resilient communities and infrastructure. The COVID-19 pandemic put enormous pressure on health systems and other infectious disease outbreaks that followed, monkeypox (Mpox), cholera, and Ebola presented devastating outcomes in populations struggling with the impact of the pandemic. These infections remain endemic in some parts of the globe. Although Mpox, cholera and Ebola have a global impact, the WHO African Region remains particularly vulnerable. Insufficient health system preparedness, effects climate change, conflicts, poverty, cultural routines and norms, and epidemic propensity of the diseases remain important aspects to deal with for a better response to the outbreaks. An integrated approach including community education and empowerment are important elements to consider for a better response to outbreaks. This chapter presents a picture on the distribution, transmission, response, and the impact of the response to the outbreaks of the diseases over time and reviews disease outbreaks and their responses during and after the COVID-19 pandemic.