In this chapter, the global epidemiological events causing infections that ravaged humanity throughout its existence by bringing hardship to rich and poor nations alike are aggregated and presented. Among these, the largest known epidemics including the recent COVID-19 pandemic will be highlighted along with the analysis of the actual and common reason behind the occurring of all the epidemic scenarios. The epidemiological and nonepidemiological impacts of the most fatal pandemics recorded in history are also discussed. The vulnerable countries’ readiness for coping with epidemics is assessed in terms of different indices. Furthermore, the current and future challenges in fighting epidemiological events are on the frontline and a number of preparative measures and strategies have been suggested.