Cardiovascular diseases and osteoporosis, seemingly unrelated disorders that occur with advanced age, share major pathogenetic mechanisms contributing to accelerated atherosclerosis and bone loss. Hyperhomocysteinemia (hHcy) is among these mechanisms that can cause both vascular and bone disease. In its more severe form, hHcy can present early in life as homocystinuria, an inborn error of metabolic pathways of the sulfur-containing amino acid methionine. In its milder forms, hHcy may go undiagnosed and untreated into adulthood. As such, hHcy may serve as a potential therapeutic target for cardiovascular disease, osteoporosis, thrombophilia, and neurodegeneration, collectively representing accelerated aging. Multiple trials to lower cardiovascular risk and improve bone density with homocysteine-lowering agents, yet none has proven to be clinically meaningful. To understand this unmet clinical need, this review will provide mechanistic insight into the pathogenesis of vascular and bone disease in hHcy, using homocystinuria as a model for accelerated atherosclerosis and bone density loss, a model for accelerated aging.