Water quality is a fundamental issue for the survival of a city, especially on dry land. In ancient times, water availability determined the location and size of villages and cities. Water supply and treatment methods were developed and perfected along with the evolution of urbanization. In Europe, after the fall of the Roman Empire, water supply and sewage systems went through fundamental changes. However, in medieval times, the lack of proper sanitation and low water quality increased the spreading and effects of epidemics. The importance of potable water quality was established during modern times. In Greece, the significance of water filtration and disinfection was not understood until the beginning of the 20th century. Moreover, the beneficial effects of water quality and sanitation on human health and especially on life expectancy are considered. In Greece and other countries, a dramatic increase in life expectancy mainly after the 2nd World War is probably due to the improvement of potable water quality and hygiene conditions. However, since the mid-20th century, new water quality issues have emerged, such as eutrophication, the improvement of water treatment technologies, as well as chemical and microbiological water pollution problems. This study, in addition to the historical evolution of water quality, highlights and discusses the current issues and challenges with regard to the management and protection of water quality, including global changes in population and urbanization, lack of infrastructure, use of nonconventional water resources, spreading of emerging pollutants and contaminants (e.g., antibiotics and microplastics), and climatic variability impacts. Against these, a review of the main proposed strategies and measures is presented and discussed to protect water quality and maintain water supplies for the future. Understanding the practices and solutions of the past provides a lens with which to view the present and future.