Today, patients undergoing dialysis are at low risk for aluminum-induced dementia. Workers are unlikely to experience cadmium-induced emphysema and the public’s exposure to lead is an order of magnitude lower than in 1970. The research field of in vivo elemental analysis has played a role in these occupational and environmental health improvements by allowing the effects of people’s chronic exposure to elements to be studied using non-invasive, painless, and relatively low-cost technology. From the early 1960s to the present day, researchers have developed radiation-based systems to measure the elemental content of organs at risk or storage organs. This reduces the need for (sometimes painful) biopsy and the risk of infection. Research and development has been undertaken on forty-nine in vivo measurement system designs. Twenty-nine different in vivo elemental analysis systems, measuring 22 different elements, have been successfully taken from design and testing through to human measurement. The majority of these systems employ either neutron activation analysis or x-ray fluorescence analysis as the basis of the measurement. In this review, we discuss eight of the successful systems, explaining the rationale behind their development, the methodology, the health data that has resulted from application of these tools, and provide our opinion on potential future technical developments of these systems. We close by discussing four technologies that may lead to new directions and advances in the whole field.