Cadmium (Cd) is a toxic heavy metal with no known biological function in plants and one of the most toxic substances released into the environment. Crops, such as rice, maize, wheat and tobacco are the major sources of Cd for humans. Cd toxicity inhibits crop growth and development by affecting many central physiological and biochemical processes, and finally it affects human health via the food chain. To adapt to Cd toxicity, crops have evolved a series of detoxification mechanisms. Immediate responses include rapid changes at the transcriptional level with simultaneous changes at the physiological and metabolic levels. However, the long-term responses involve genetic modifications and epigenetic changes. During the last decade, many genes involved in Cd uptake and translocation have been identified, and many of them are transporters. To decrease the accumulation of Cd in cereal grains and tobacco leaves, a number of approaches have been proposed, including physical and chemical methods, developing and planting low accumulation genotypes using transgenic strategies or marker–trait association breeding. In this review, we describe the toxicity of Cd to crops and human body, advances in the molecular mechanisms of Cd accumulation in cereal crops and tobacco, and approaches to decrease Cd accumulation.