Abstract: Abnormally high uranium (U) prevalence in groundwater is a neoteric subject of concern throughout the world because of its direct impact on human health and well-being. Groundwater is used as the most preferred choice for drinking because of its good quality and ease of availability in rural and urban parts of India, and also in different parts of the world. India is an agriculture-dominant country and its 50–80% irrigational requirement is met by groundwater, besides this nearly 90% of rural and 50% of urban water needs are fulfilled by groundwater. The uranium concentration in groundwater in different parts of India namely Punjab, Haryana, Rajasthan, Madhya Pradesh, Karnataka, etc. found to be varying from 0 mg/L to 1443 mg/L, and in different parts of the world, it is found up to 1400 mg/L in the countries like United States, Canada, Finland, Mongolia, Nigeria, South Korea, Pakistan, Burundi, China, Afghanistan, etc. Various natural factors such as geology, hydro-geochemistry, and prevailing conditions as well as anthropogenic factors including mining, nuclear activities, erratic use of fertilizers, and overexploitation of groundwater resources are responsible for adding uranium in groundwater. Groundwater is considered a primary source of uranium ingestion in human beings as it contributes 85% while food contributes 15%. Uranium affects living beings as a two-way sword, being a radioactive element, causing radiotoxicity, and on the other hand as a heavy metal, it causes chemotoxicity. The main target organs affected by the consumption of uranium-contaminated water are kidneys, bones, lungs, etc. It can cause renal failure, impair cell functioning and bone growth, and mutation in DNA. Although, its toxic effects, being a heavy metal, are more severe than its radiotoxicity. Various techniques are available for the efficient removal of uranium from the groundwater such as bioremediation, nanotechnology-enhanced remediation, adsorption, filtration, etc. This chapter entails a comprehensive investigation of uranium contamination in groundwater of rural and urban parts of India their probable sources, health impacts, treatment, and mitigation techniques available to manage groundwater resources.