Magnesium plays an important role in many physiological functions. Habitually low intakes of magnesium and in general the deficiency of this micronutrient induce changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases. The assessment of magnesium status is consequently of great importance, however, its evaluation is difficult. The measurement of serum magnesium concentration is the most commonly used and readily available method for assessing magnesium status, even if serum levels have no reliable correlation with total body magnesium levels or concentrations in specific tissues. Therefore, this review offers an overview of recent insights into magnesium from multiple perspectives. Starting from a biochemical point of view, it aims at highlighting the risk due to insufficient uptake (frequently due to the low content of magnesium in the modern western diet), at suggesting strategies to reach the recommended dietary reference values, and at focusing on the importance of detecting physiological or pathological levels of magnesium in various body districts, in order to counteract the social impact of diseases linked to magnesium deficiency.