Disorders of essential elements arise from inadequate intake, genetic defects, excessive exposure, or impaired elimination. Severe deficiency is rare, but aspecific symptoms and reduced protection against risk factors have been ascribed to suboptimal intake of trace elements. Inherited disturbances of the metabolism of copper, zinc, and molybdenum determine severe diseases, which may have fatal outcomes. Besides occupational and environmental exposure, metal toxicity has been reported in clinical conditions such as parenteral nutrition and hemodialysis. The prevention, diagnosis, and monitoring of pathological conditions related to trace elements, as well as pharmacokinetic studies of metallodrugs and therapy monitoring, rely mainly on the dosage of metals in appropriate compartments, such as blood, urine, and tissues (hair, nails, biopsies, and postmortem samples). However, appropriate compartments may not always be amenable for sampling, and determination of the total amount of an element may not be informative or may even be misleading if the compartment volume also undergoes changes or the different chemical forms of the element vary in opposite directions. New biochemical tests may become available for the prevention, diagnosis, and monitoring of disorders of trace elements as analytical techniques gain improved detection and resolution power. In particular, interest is focused on the dosage of biologically active elemental species and the application of stable isotopes in tracer studies.