Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease of the nervous system. There has been mounting evidence showing that MS is associated with increased risk of osteoporosis and fractures. The development of osteoporosis in MS patients can be related to the cumulative effects of various factors. This review summarizes the common risk factors and physiologic pathways that play a role in development of osteoporosis in MS patients. Physical inactivity and reduced mechanical load on the bones (offsetting gravity) is likely the major contributing factor for osteoporosis in MS. Additional possible factors leading to reduced bone mass are low vitamin D levels, and use of medications such as glucocorticoids and anticonvulsants. The role of the inflammatory processes related to the underlying disease is considered in the context of the complex bone metabolism. The known effect of different MS disease-modifying therapies on bone health is limited. An algorithm for diagnosis and management of osteoporosis in MS is proposed.