Osteoporosis is a bone disease characterizedlow bone mass and deteriorated bone microstructure, which could be related to the disorders of energy metabolism and bone senescence. Silent mating-type information regulator 2 homolog 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that regulates cell senescence, energy metabolism and bone remodeling. SIRT1 could be activated not onlyadenosine 5-monophosphate (AMP)-activated protein kinase (AMPK), c-Jun N-terminal kinase 1 (JNK1) and casein kinase 2 (CK2), but alsosmall-molecular drugs such as resveratrol. All these kinases and drugs can affect bone metabolism. Recent findings indicate that SIRT1 signaling pathway plays a direct role in bone metabolism, but the underlying mechanism remains unclear. This paper reviews the structure and function of SIRT1, and the role of SIRT1 in bone metabolism, and discusses the potential of SIRT1 signaling pathway as a new therapeutic target in osteoporosis.