Introduction: Bisphosphonates are the first-choice treatment for osteoporosis. They effectively increase bone mineral density, reduce markers of bone resorption, and lower the incidence of new fractures in patients with osteoporosis-related fracture. However, the efficacy observed in clinical trials may not be realized in a real-life setting, partly due to poor adherence to therapy, with a significant worsening of clinical outcomes. Several issues contribute to poor adherence to osteoporosis medication, including inconvenient dosing regimens and concerns about possible adverse events. Although strategies to improve adherence have been investigated, new approaches are required. Areas covered: We review available data and propose a new approach to improve adherence to osteoporosis therapy in clinical practice. We present the current evidence and personal experience from a group of Italian osteoporosis experts. Expert opinion: To improve adherence, we propose a multifaceted approach, which includes the Triad Model suggested by the World Health Organization, direct observed therapy and the use of drugs with longer administration intervals, e.g., zoledronic acid. The integration of these strategies may provide the basis for a marked increase in adherence to osteoporosis therapy, and improved clinical outcomes in a real-life scenario. © 2011 Informa UK, Ltd.