Chemical contamination of drinking water (including salinity) puts more than one billion people at risk of adverse health effects globally. Resource-constrained communities are the most affected and face unique challenges that require innovative safe water solutions. This review focuses on arsenic, fluoride, nitrates, lead, chromium, total dissolved solids, emerging organic contaminants, and, to a lesser extent, manganese, cadmium, selenium, and uranium. It covers contaminant prevalence, major health effects, and treatment technologies or avoidance strategies that have been proven effective in realistic water matrices and conditions. The review covers the levelized costs of water for pilot- and full-scale systems most relevant to resource-constrained communities, with a focus on component costs including the costs of power systems, lifting water, waste management, and labor. These costs are not universally reported, but can be significant. The findings are analyzed and discussed in the context of providing sustainable safe water solutions in resource-constrained settings. Expected final online publication date for the Annual Review of Environment and Resources, Volume 45 is October 19, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.