Blood lycopene concentration, which is usually used as a marker of lycopene status, is affected by numerous factors, e.g., lycopene intake, lycopene absorption efficiency, and lycopene metabolism. These factors can in turn be modulated by genetic variations in the proteins involved in lycopene absorption and metabolism. Recent studies support this hypothesis. Indeed, some genetic variants (only single nucleotide polymorphisms have been studied so far) have been associated with both fasting and postprandial blood lycopene concentrations. The effects of the identified genetic variants on blood lycopene concentration are relatively low, i.e., each genetic variant usually modulates only a few percentage points of the phenotype, but it has been shown that the additive effect of several genetic variants can modulate a significant fraction of lycopene bioavailability. However, a lot of work remains to be done to identify, and to replicate in different populations, all the genetic variants identified, to assess the possible involvement of other kinds of genetic variation, e.g., copy number variants and epigenetic modifications, in order to establish a reliable list of genetic variations that will allow us to predict the lycopene status of an individual. Yet, the potential usefulness of this area of research is exciting with regard to personalized nutrition and for future clinical trials dedicated to assessing the biological effects of lycopene.