Humans acquire vitamin D through skin photosynthesis and digestive intake. Two hydroxylations are needed to obtain the bioactive compound, the first produces 25-hydroxyvitamin D [25(OH)D], and the second 1,25-dihydroxyvitamin D [1,25(OH)2D]. There is no consensus regarding the appropriate cut-off level to define the normal serum 25(OH)D range. Experimental, epidemiological and clinical studies have related low vitamin D status with longevity. Although some results are controversial, low serum 25(OH)D levels have been linked to all-cause, cardiovascular, cancer and infectious related mortality. Throughout life span a significant proportion of human beings display insufficient (20-30 ng/mL) or deficient (<20 ng/mL) serum 25(OH)D levels. Appropriate lifestyle changes, such as regular short exposures to sunlight (15 min a day), and an adequate diet that includes vitamin D rich components, are not always easily accomplished. Studies relating to vitamin D supplementation have methodological limitations or are based on relatively low doses. Therefore, dosages used for vitamin D supplementation should be higher than those traditionally suggested. In this sense, there is an urgent need for prospective controlled studies using high daily vitamin D doses (2,000 IU or higher) including cardiovascular, cancer, infectious and other endpoints. Relationship between vitamin D and health outcomes is not linear, and there are probably various optimal vitamin D levels influencing different endpoints.