Soil can exert both positive and negative impacts on human health. In this paper, three aspects of the relationship between soil and human health are discussed: 1) supply of essential mineral nutrients from soil to humans; 2) human’s exposure to toxic heavy metals and metalloids via their transfer from soil to the food chain; and 3) the spread of antibiotic resistance genes in soil. Although soils, through the food chain, are a main source of many essential mineral nutrients for humans, for some nutrients the supply may not meet the requirements of humans, especially those elements that are required by animals but not by plants. Selenium is a typical example, which is deficient in the diets of many people due to low levels of this element in the soil. Agronomic biofortification through additions of selenium in fertilizers is an effective way to increase selenium intake in the population living in the low selenium areas. Human activities have caused contamination of soil with various types of organic and inorganic contaminants. Heavy metals and metalloids such as cadmium and arsenic can be transferred readily from soil to the edible organs of crop plants, posing a risk to human health. Soil contamination coupled with soil acidification has resulted in increased availability of cadmium in soil and elevated accumulation of this toxic metal in food crops. A number of strategies can be used to reduce the accumulation of heavy metals and metalloids in food crops, including methods to immobilize contaminants in soil, cultivar selection, breeding and genetic engineering to reduce heavy metal uptake or translocation in crop plants, phytoextraction of heavy metals and metalloids with hyperaccumulators to clean up contaminated soil. Overuse of antibiotics in humans and in animal production has resulted in increased antibiotic resistance in microorganisms in the environment, which may lead to the evolution of superbugs of human pathogens. Animal manures may contain high levels of antibiotic resistant microbes and resistance genes, which can disseminate into agricultural soil via manure applications. Urgent actions should be taken to control the overuse of antibiotics in animal production. Effective methods are also needed to decrease the abundance and diversity of antibiotic resistance microbes and genes in animal manures before application to soil. It is recognized that the impacts of soil on human health are uneven across the whole population; people living in poor areas or having a low income are often more vulnerable to the negative effects of soil on human health. The relationship between soil and human health will become more prominent in the future with the dual challenges of increasing population and global climate changes. Options to alleviate the negative impacts of soil on human health and future research directions are also discussed.