Water is vital for billions of people, but its quality and availability are threatened globally. Increasing pollution, overuse, and climate change are straining precious water resources. Thus mitigating contamination of water resources is vital for achieving the UN’s Sustainable Development Goal for universal access to safe drinking water by 2030. This chapter discusses the challenges of water contamination from both natural and human-induced factors, with a special focus on groundwater resources, as groundwater is a major source of drinking water in numerous populous countries. It highlights the varying issues of safe groundwater accessibility in different regions of the world, with detailed case studies on groundwater water contamination from Tanzania, India, Bolivia, and Bangladesh.