Although the RCT may be the “king” of study designs, 1 RCT is rarely definitive. The first published rhBMP-2 trial (n = 14) reported that disability scores improved sooner with rhBMP-2 than with bone graft, quality of life improved, and no adverse events occurred (6). Although few would consider the results of this small, initial trial as a solid basis for treatment decisions, some may rely on the largest, later trial. That trial (n = 577) reported that rhBMP-2 improved outcomes, including function, pain, and return to work (7). Yet, after systematic evaluation and synthesis of all available evidence, both systematic reviews published here independently conclude that rhBMP-2, compared with iliac crest bone grafting, does not improve pain or function and increases adverse events, possibly including cancer (1–2). For the outcome of fusion, the focus of initial enthusiasm for rhBMP-2, 1 review concluded that it improved by a marginally statistically significant amount with rhBMP-2 (overall fusion, 1.14 [95% CI, 1.03 to 1.25]), and the other concluded that it did not (anterior fusion, 1.05 [CI, 0.88 to 1.24]; posterior fusion, 1.16 [CI, 0.96 to 1.41]). Of importance, the CIs for both sets of estimates substantially overlap, and neither review found differences in pain or function, the outcomes that reflect patients’ well-being.