It has been over 2 years since parathyroid hormone (PTH 1–34) was approved in the US and Europe for the treatment of osteoporosis in postmenopausal women and men. Clinical experience with this peptide has enhanced confidence in its use and its application in specific clinical scenarios. There is no doubt that PTH 1–34 is safe and effective in reducing spine and non-vertebral fractures in men and women. However, the lack of several randomized placebo-controlled trials and their relatively short duration raise several questions that still need to be answered. This paper reviews three major areas of uncertainty: (1) Is there significant heterogeneity in the bone density response of individuals to PTH? If so, what factors are important predictors? (2) What other regimens are available for PTH use? (3) What, if anything, should the clinician do after PTH is discontinued? Answers to these questions will undoubtedly lead to even greater utilization of this drug and some of its future derivatives.