The sense of smell is a complex molecular device, encompassing several hundred olfactory receptor proteins (ORs). These receptors, encoded by the largest human gene superfamily, integrate odorant signals into an accurate ‘odor image’ in the brain. Widespread phenotypic diversity in human olfaction is, in part, attributable to prevalent genetic variation in OR genes, owing to copy number variation, deletion alleles and deleterious single nucleotide polymorphisms. The development of new genomic tools, including next generation sequencing and CNV assays, provides opportunities to characterize the genetic variations of this system. The advent of large-scale functional screens of expressed ORs, combined with genetic association studies, has the potential to link variations in ORs to human chemosensory phenotypes. This promises to provide a genome-wide view of human olfaction, resulting in a deeper understanding of personalized odor coding, with the potential to decipher flavor and fragrance preferences.