Beyond providing energy through its high starch content, the potato tuber can make a significant contribution to the dietary intake of certain minerals including potassium, phosphorous, magnesium and iron, as well as of vitamin C, dietary fibres and phenolic compounds. While some animal and human studies have shown beneficial associations between the consumption of potato, or some of its components, and health, some other studies could not confirm these positive effects. Numerous factors may indeed influence (i) the composition of the potato tuber itself, i.e. genotype, environmental conditions during growth, post-harvest storage conditions, cooking and processing, and (ii) the bioaccessibility and bioavailability of its components, affecting the final bioactivity. The purpose of this paper is to provide a brief overview of potato composition variability followed by an analysis of potential health-promoting effects and bioavailability of specific components including iron and phenolic compounds. It appeared that the various components of the potato matrix might interact with each other at the intestinal level, leading to favourable or detrimental effects on their bioavailability. The consumption of a potato cultivar with a high level of phenolic compounds may improve the health status of an individual regarding its risk of developing chronic diseases on the one hand, but may reduce iron absorption on the other hand, putting an individual at risk of micronutrient deficiency. Tailoring potato varieties or products to match the population nutritional needs appears therefore of major importance.