Osteoporosis is a prevalent disease, particularly among postmenopausal women, characterized by low bone mass and increased skeletal fragility. It is a complex disease resulting from the interaction of hereditary and environmental factors. Many investigators have studied the genetic influence on bone mass. Although the results have been controversial and not reproduced consistently, some genes appear to be likely candidates, including those related to estrogen metabolism and activity. According to their effects on bone remodeling, anti-osteoporotic drugs can be classified as anticatabolic (estrogens, selective estrogen receptor modulators, bisphosphonates, calcitonin, vitamin D, calcium) or anabolic (parathyroid hormone and derivatives). These drugs increase bone mineral density and may reduce fracture rate. There are few data about the influence of the individual genetic characteristics on the response to anti-osteoporotic drug therapy. Nevertheless, a number of studies suggest that some polymorphisms of estrogen and vitamin D receptors may be associated with differences in the changes of bone mineral density induced by anticatabolic agents. However, there is a clear need of further investigations before genetic data can be used in clinical practice to individualize drug use in the prevention and treatment of osteoporosis.