Osteoporosis is a worldwide health problem related to the aging of the population, and it is often underdiagnosed and undertreated. It is related to substantial morbidity, mortality and impairment of the quality of life. Estrogen deficiency is the major contributing factor to bone loss after menopause. The lifetime fracture risk at 50 years of age is about 50% in women. The aim of the treatment of osteoporosis is to prevent fractures. Non-pharmacological treatment involves a healthy diet, prevention of falls, and physical exercise programs. Pharmacological treatment includes calcium, vitamin D, and active medication for bone tissue such, as anti-resorptives (i.e., SERMs, hormonal replacement therapy, bisphosphonates, denosumab), bone formers (teriparatide), and mixed agents (strontium ranelate). Bisphosphonates (alendronate, risedronate, ibandronate, and zoledronate) are the most used anti-resorptive agents for the treatment of osteoporosis. Poor compliance, drug intolerance, and adverse effects can limit the benefits of the treatment. Based on the knowledge on bone cells signaling, novel drugs were developed and are being assessed in clinical trials.