Human beings have been struggling against epidemics for centuries but the first recorded epidemic in Egypt goes back to 3180 BC. Historically, it was not recognized that many of these "plagues" were waterborne. Advancements in medicine and microbiological sciences which identified and isolated the pathogens were needed before "safer" water could be achieved through advances in engineering. Disinfection of drinking water, introduced at the end of 19th century, considerably reduced the spread of cholera and typhoid fever. However, despite these innovations, waterborne disease epidemics continue even in the 20th century. We contend that this is partly because little attention has been paid to sewage practices and these are directly related to our health as the source of contamination, while much attention has been focused on drinking water. We propose that to achieve "safe water" and an improvement in global health worldwide in the 21st century, we must address wastewater problems learning from the past and we must use new advances such as molecular microbiology for pathogen discovery, and characterization and control of emerging and re-emerging waterborne diseases.