The book chapter provides a brief survey of the clinical role of essential and nonessential heavy metals for treating disease and maintaining health. Both forms of heavy metals have a long history as medicinal products to cure human diseases, while indication for the treatment of specific disorders was found for 27/32 heavy metals, ranging from aluminum to zinc. However, their clinical use is nowadays restricted to a few ones due to a lack of evidence based on therapeutic efficacy or because of substitution by other chemical medicines with a positive ratio of benefits versus risks as based on results of randomized controlled trials (RCTs). Promising are heavy metals like gold, silver, platinum, palladium, titanium, copper, iron, and zinc if used as nanoparticles (NPs) ranging from 1 to 100 nm in size. They can become part of personalized therapy approaches for malignancies in the context of cancer drug resistance. Therapeutic cytotoxic effects of metallic NPs are initiated through the generation of reactive intermediates, which lead to oxidative stress within mitochondria or endoplasmic reticulum, representing the microsomes, DNA damage, cell cycle arrest, and finally to apoptotic/necrotic cell death or autophagy. Their therapeutic efficacy can be enhanced if combined with antibodies, DNA, RNA, peptides, and proteins. Issues of biosensing, catalysis, and bioimaging are strongly associated with the properties on NPs. NPs traffic to the spleen and lymph organs with their relevant immune cells, making them good candidates for the delivery of immunotherapeutic agents. For maintaining health, various essential heavy metals in low amounts are responsible. However, heavy metals are potentially toxic in high amounts in a dose-dependent way, while nonessential ones are injurious even in small concentrations.