A perspective of epidemics and pandemics in Mexico is offered, focusing on three time periods, namely, end of the 18th century, the 20th century, and the 21st century, in order to analyze how they were approached by health and government authorities, as well as the challenges they have represented. Historical documentary sources were consulted and, in current cases, participation in them was analyzed. Epidemiological and social historical methodologies were combined. The presence of epidemics in Mexico is a constant on its evolution, which highlights the need for the epidemiological surveillance system to be updated, the importance of being prepared to face an epidemic and to develop a contingency plan.