Postmenopausal osteoporosis is a chronic progressive condition characterized by reduced bone mass and impaired bone quality, leading to an increased risk of fragility fractures. Osteoporotic fractures reduce quality of life and are associated with high morbidity, mortality and economic burden. Primary and secondary prevention interventions are always recommended starting from the premenopausal age, in women after menopause, however, it is essential to develop a long-term intervention strategy that allows to identify patients at high risk of fracture and the choice of therapy based on the estimated risk. This narrative review described the tools for layering the management approach in relation to low, high and very high fracture risk. Several medications are now available for the treatment of osteoporosis and the prevention of fractures; the knowledge of the efficacy, safety and additional benefits profile of the individual preparations allows an appropriate choice between the different drugs available and the possibility of adapting the prescription to the lifetime fracture risk spectrum. From the literature it emerges that menopausal hormone therapy (MHT), TSEC combination and SERMs can be drugs of choice to counteract postmenopausal bone loss in younger women or at low risk of fracture, while bisphosphonates and denosumab are appropriate for women with high risk or at an older age. Therapy with denosumab and anabolic agents such as teriparatide and romosozumab is particularly indicated for subjects with very high risk of fracture.