In this paper we present a comparative assessment of drinking-water standards from almost all South American countries, using the USA and the Canadian standards and the World Health Organization (WHO) Guidelines as references. Similarities and discrepancies between standards/guidelines were identified through descriptive analyses and, in the case of chemical standards, clustering techniques. In general, one or another of the four consecutive editions of the WHO Guidelines were shown to be quite influential in setting drinking-water standards in the region, but not so much the USA and the Canadian standards. Considerable discrepancies between South American drinking-water standards were found, mainly with respect to chemical substances. Questions are raised about their scientific basis and/or the practicalities for their enforcement. In conclusion, the paper highlights that many drinking-water regulations in South America need updating, taking on the approach of health-based targets in setting these standards, as well as that of a broader risk-based preventive management in the entire supply system to assure water safety.