Abstract Background: Climate change is the “biggest global health threat of the twenty-first century; many observers expect that earth will warm to at least 2 °C (3.6 °F) over the preindustrial average; rainfall patterns will change; extreme weather events will become more frequent; sea levels will rise, with increased flooding in coastal areas; and so forth. Such changes may have serious repercussions for children and families worldwide. Climate change entails a wide variety of public health risks, authorities and other stakeholders thus need to understand current and projected impacts of climate change and their implications for health to prepare and implement a variety of responses to ensure an optimal level of adaptation. Examples of such responses include early warning systems, emergency management plans and provisions and health systems strengthening; other preventive measures include safer housing, flood protection, vector control, and improved surveillance. Objectives: (a) To review the direct and indirect impact of climate change on health, (b) to provide evidence of climate change and related infectious diseases, (c) to highlight on the serious diseases correlated with climate extremes, (d) to provide an evidence for estimating disease burden and risk factors correlated with climate change, and (e) to review climate change health impacts on developed and developing countries with more focus on middle East. Methodology: This paper uses a systematic review of different studies and journal articles addressing climate change issue, besides reviewing the publications addressed by global and international health institutions and organizations, such as WHO Organization, CDC, and NIH. Findings are synthesized, summed up, and interpreted to generate the evidence. Different key words were used to synthesize the inputs, such as climate change, infectious diseases, developing countries, developed countries, Middle East, and burden of disease. Key findings: Climate change is expected to cause approximately 250,000 additional deaths per year between 2030 and 2050, approximately 87 million people were displaced due to extreme weather events between 2008 and 2011. WHO estimates that every year about 150,000 deaths occur worldwide in low-income countries due to adverse effects of climate change, such as malnutrition, floods, diarrheal diseases, and malaria. FAO estimates that by 2030, up to 122 million more people could be forced into extreme poverty because of climate change. Direct health effects will be temperature-related illness and death, extreme weather-related health effects, and airborne-related health effects. Indirect health effects are water and foodborne, vector-borne, and rodent borne diseases, food and water shortage, and nutritional and mental health effects. Excess mortality due to heat waves is greatest in the elderly and those with low immunity. This mortality occurs because of CVD or cerebrovascular or respiratory diseases. Winter mortality was reported to be 10–25% higher than those in summer, due to CVD, circulatory and respiratory diseases, and influenza outbreaks. In terms of Burden of disease, measured by DALYs, climate change is estimated to have caused the loss of over 150,000 lives and 5,500,000 DALYs (0.3% of deaths and 0.4% of DALYs, respectively). The Middle East is going to experience climate change threatening basic life, due to reduced surface water hitting agriculture and resulting in crop failure and might lead to starvation and poverty. Lack of available drinking water will increase cholera and other waterborne diseases. The government could respond by importing more water at a financial cost but also an environmental one, as it requires transport, causing again the release of CO2. UAE has one of the highest levels of GHG emissions per capita; however, there are only limited impacts on infectious and diarrheal diseases in the UAE due to relatively low baseline levels of these climate-sensitive diseases. The major impacts of climate change in the UAE are expected to be increased heat stress. Conclusion: Climate change has enormous and diverse effects on human health. Rises in temperature and sea level and extreme weather events such as floods cause water logging and contamination, which in turn exacerbate diarrheal diseases. Vector-borne diseases and other communicable disease will be the result of climate change. Poor and poorer nations will be more impacted due to fragile health systems and resources.