Recent developments in frequency metrology and optical clocks have been based on electronic transitions in atoms and singly charged ions as references. The control over all relevant degrees of freedom in these atoms has enabled relative frequency uncertainties at a level of 10(-18). This accomplishment not only allows for extremely accurate time and frequency measurements, but also to probe our understanding of fundamental physics, such as a possible variation of fundamental constants, a violation of the local Lorentz invariance, and the existence of forces beyond the standard model of physics. In addition, novel clocks are driving the development of sophisticated technical applications. Crucial for applications of clocks in fundamental physics are a high sensitivity to effects beyond the standard model and a small frequency uncertainty of the clock. Highly charged ions offer both. They possess optical transitions which can be extremely narrow and less sensitive to external perturbations compared to current atomic clock species. The large selection of highly charged ions offers narrow transitions that are among the most sensitive ones for the "new physics" effects. Recent experimental advances in trapping and sympathetic cooling of highly charged ions will in the future enable advanced quantum logic techniques for controlling motional and internal degrees of freedom and thus enable high-accuracy optical spectroscopy. Theoretical progress in calculating the properties of selected highly charged ions has allowed the evaluation of systematic shifts and the prediction of the sensitivity to the physics beyond the standard model. New theoretical challenges and opportunities emerge from relativistic, quantum electrodynamics, and nuclear-size contributions that become comparable with interelectronic correlations. This article reviews the current status of the field, addresses specific electronic configurations and systems which show the most promising properties for research, their potential limitations, and the techniques for their study.