This review illustrates the state of air, water and soil pollution with heavy metals resulting from mining activities in the cross-border area of Romania and the Republic of Serbia. It also emphasizes the possible human health effects that certain heavy metals can cause. The heavy metals that were identified as polluting the air, water, and/or soil in the area of interest are: As, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, and Zn. Acute or chronic exposure to these heavy metals may cause numerous human health effects as they affect numerous organs and tissues (gastrointestinal tract, liver, lungs, kidneys, bladder, central nervous system, reproductive system, etc.). The review shows that the pollution produced by both abandoned and active mines cannot be neglected and underlines the necessity of changes in the current mining practices so that mining operations will assure better protection for the environment and human health.