Obesity, diabetes, and osteoporosis are major public health concerns. Current estimates indicate that the US population consists of 25% obese, 30% diabetic and prediabetic, and, among the elderly, 50% of all osteoporotic individuals. Mechanistically, these pathologies share several features including common regulators of bone homeostasis and energy metabolism. Peroxisome proliferator-activated receptors (PPARs) represent a family of proteins that control energy turnover in adipose, liver, and muscle tissue. These proteins also control bone turnover and regulate bone cell differentiation. Recent evidence suggests that bone is an organ integral to energy metabolism not only with respect to energy storage, but also as an organ regulating systemic energy homeostasis. In this article, we review current knowledge on the role of PPARs in bone metabolism and bone cell differentiation. We also discuss the role of bone fat in modulation of bone marrow microenvironment and its possible contribution to the systemic regulation of energy metabolism.