Heavy metals are prominent environmental contaminants that originate from either or both the natural and anthropogenic sources—agriculture, domestic, and industrial sectors. Heavy metals such as Zinc (Zn), Manganese (Mn), Iron (Fe), Cobalt (Co), Molybdenum (Mo), Copper (Cu), Selenium (Se), and others are essential to human physiology in the form of micronutrients but can be toxic in higher quantities, whereas the heavy metals like Mercury (Hg), Arsenic (As), Cadmium (Cd), and Lead (Pb) are harmful and non-essential even in trace quantities. The harmful effects of any heavy metal are characterized by its concentration, period, and route (inhalation, ingestion, and dermal contact) of the exposure. They can accumulate in the human body to pose lethal effects on different organs such as the brain, kidney, and liver to eventually damage them. The mechanism, followed by an average heavy metal, features the action of oxidative stress by developing different Reactive Oxygen Species (ROS) inside the cell and the mitochondria. These ROS, directly or indirectly, interrupt several key cellular processes that eventually lead to cell death, tissue damage, and organ failure. There is a dire need of the hour to address the alarming condition followed by heavy metal toxicity in different body organs. Thus, the chapter describes the heavy metals or metalloids, their route of exposure, and their lethal impact on various human organs by highlighting their pharmacokinetic processes.