Trace metal analysis has been long regarded as one of the principle tasks in areas of chemical analysis. At the early stage of instrumental development, total concentration was assessed in a variety of samples, yielding results, among others, for environmental, biological, and clinical samples. With the power of newer analytical techniques, such as inductively coupled plasma mass spectrometry (ICP-MS), accurate quantitative results can now be obtained at ultra-trace levels not only for metals, but also for metalloids and several non-metals. Even though the importance of trace elements in many biological processes is widely accepted, the elucidation of their biological pathways, understanding specific biological functions, or possible toxicological aspects is still a challenge and a driving force to further develop analytical methodology. Over the past decades, the scientific interest has moved from total element determination to include speciation analysis, which provides quantitative information of one or more individual element species in a sample. More recently, metallomics has been introduced as a more expanded concept, in which the global role of all metal/metalloids in a given system is considered. Owing to the multi-elemental focus of metallomics research, the use of ICP-MS becomes indispensable. Furthermore, considering the biological role of metals/metalloids and the use of elements as internal or external molecular tags, epigenetics should be considered as an important emerging application for metallomics studies and approaches. Among a variety of epigenetic factors, essential nutrients, but also environmental toxins, have been shown to affect DNA methylation, modification of histone proteins, and RNA interference, all of them being implicated in cancer, cardiovascular disease, and several inherited conditions. Recent studies suggest that epigenetics may be a critical pathway by which metals produce health effects. In this Trends article, the basic epigenetic concepts are introduced, followed by the early applications of ICP-MS classified as: (i) detection of (31)P as a natural element tag for DNA, (ii) analysis of DNA adducts with metal-based drugs, (iii) element species as epigenetic factors.