<p>Osteoporosis is a systemic disease characterised by reduced bone mineral density and a degradation of bone microarchitecture, ultimately resulting in an increased risk of fragility fractures. Anti-osteoporotic therapies encompass both antiresorptive and anabolic treatments, which are effective in preventing fractures; however, they are also associated to potential adverse events that may impact on a patient’s clinical status. The most noteworthy complications of antiresorptive therapy include osteonecrosis of the jaw and atypical femoral fractures, both of which are related to extended treatment duration and the presence of predisposing factors. Oral bisphosphonates may also lead to gastro-oesophageal disorders, whereas intravenous administration is linked to acute phase reactions and, less frequently, nephrotoxicity and atrial fibrillation. Hypocalcaemia is another rare but potentially severe complication of antiresorptive treatment, particularly in patients with vitamin D deficiency or chronic kidney disease. Anabolic treatment, including teriparatide, abaloparatide, and romosozumab, typically exhibit a favourable safety profile; however, romosozumab may be linked to an increased cardiovascular risk in patients with predisposing factors. An in-depth comprehension of the possible complications associated with anti-osteoporotic therapies is crucial for a detailed risk-benefit evaluation and a patient-tailored treatment. A careful therapeutic selection and a regular monitoring for potential adverse events are crucial for ensuring safety, efficacy, and adherence to treatment in patients with osteoporosis.</p>