The role of prostaglandin E2 (PGE2) in the regulation of bone remodeling is well established. There is increasing evidence that various long-chain polyunsaturated fatty acids (LCPUFAs), as well as nonprostanoid LCPUFA metabolites, also have critical roles in regulating bone metabolism and may have therapeutic potential in the management of postmenopausal osteoporosis. Although only the 18-carbon precursors for the n-3 and n-6 LCPUFAs are deemed "dietary essential," the ability of the body to convert these precursor fatty acids into the more highly unsaturated 20- and 22-carbon LCPUFAs decreases with aging, menopause, and various lifestyle factors (e.g., smoking). Increasing dietary LCPUFA intake increases tissue and blood LCPUFA concentrations, as well as the concentrations of their metabolites. Modification of dietary LCPUFA content, particularly increasing the intake of n-3 LCPUFAs, has been shown to minimize the decline in bone mass caused by menopause in women and ovariectomy in animal models. This review summarizes findings from both in vivo and in vitro studies and outlines the effects of LCPUFAs and their metabolites on calcium balance, osteoblastogenesis, osteoclastogenesis, and osteoblast and osteoclast function.