In comparison with calcium, magnesium is an “orphan nutrient” that has been studied considerably less heavily. Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer. Almost half (48%) of the US population consumed less than the required amount of magnesium from food in 2005–2006, and the figure was down from 56% in 2001–2002. Surveys conducted over 30 years indicate rising calcium-to-magnesium food-intake ratios among adults and the elderly in the United States, excluding intake from supplements, which favor calcium over magnesium. The prevalence and incidence of type 2 diabetes in the United States increased sharply between 1994 and 2001 as the ratio of calcium-to-magnesium intake from food rose from <3.0 to >3.0. Dietary Reference Intakes determined by balance studies may be misleading if subjects have chronic latent magnesium deficiency but are assumed to be healthy. Cellular magnesium deficit, perhaps involving TRPM6/7 channels, elicits calcium-activated inflammatory cascades independent of injury or pathogens. Refining the magnesium requirements and understanding how low magnesium status and rising calcium-to-magnesium ratios influence the incidence of type 2 diabetes, metabolic syndrome, osteoporosis, and other inflammation-related disorders are research priorities.