Oral Bisphosphonates (BPs) are the mainstay of osteoporotic treatment, however long-term adherence remains a challenge, primarily owing to the chronic character of the disease and the regimen complexity. Poor compliance has been shown to have a clear link to fracture risk. The role of bone turnover markers (BTMs) as a tool to ascertain adherence and response to therapy is supported by their rapid response to treatment; a decrease in values is witnessed within days or weeks of commencing treatment. A greater reduction of serum CTX and NTX is evidenced with alendronate and ibandronate compared to risedronate. A change in bone formation BTMs appears to be related to vertebral fracture risk reduction, whereas no significant relationship is evident for hip and non-vertebral fractures. The utility of BTMs as an adjunct for monitoring withdrawal of treatment with oral BP has also been suggested. Finally, studies evaluating BTMs as an intervention, failed to demonstrate any effect on adherence. This review explores the challenge of long-term adherence with bisphosphonates and provides an analytic framework with respect to the role of BTMs in monitoring bisphosphonate treatment, adherence and the offset of treatment effect.