Some olfactory receptors (ORs) are expressed in non-nasal tissues and activation of these receptors stimulates tissue-specific functions activating intracellular signaling pathways. It has been reported that the ORs in extra-nasal tissues could regulate energy metabolism and cancers and more recent findings showed that ORs can also be involved in the regulation of cellular aging process. In energy metabolism, the function of Olfr544 has been intensively studied. Olfr544 increases adipose lipolysis and hepatic fatty acid oxidation thus reduces adiposity. In skeletal muscle, Olfr544 increased mitochondrial biogenesis and, in enteroendocrine cells, Olfr544 increases GLP-1 and cholecystokinin secretion modulating eating behavior. The expression of ORs are altered in several cancers compared with levels in non-cancerous tissues and play critical antitumor functions. For example, OR51E2 is upregulated in several cancers including prostate cancer cells but is downregulated in colorectal cancer cells compared to those of non-cancerous cells. The ligand of OR51E2, β-ionone, inhibits anticancer activity in these cancer cells. In colorectal cancer cells, activation or OF51E2 increases intracellular calcium concentrations and suppress MEK-ERK signaling axis thus suppresses tumorigenesis. Alternatively, recent findings suggest that ORs are involved in the regulation of cellular senescence in keratinocytes, myotubes, and colorectal cancer cells. Collectively, these findings suggest that ORs have diverse functions and could regulate energy metabolism, cancer, aging processes in multiple tissues.