Magnesium plays a fundamental role in many cellular functions, and thus there is increasing interest in its role in clinical medicine. Although numerous experimental studies indicate positive effects of magnesium in a variety of disease states, large clinical trials often give conflicting results. However, there is clear evidence for magnesium to benefit patients with eclampsia or torsades de pointes arrhythmias. In addition, magnesium seems to have antinociceptive and anesthetic as well as neuroprotective effects, yet well-designed large clinical trials are required to determine its actual efficacy in pain management or in the state of stroke or subarachnoid hemorrhage. The current review aims to provide an overview of current knowledge and available evidence with respect to physiologic aspects of magnesium and proposed indications and recommendations for its use in the clinical setting.