Background: Targeted therapy has revolutionized the treatment of mRCC. However, cost has lead to variable regional approval and funding. Can such variation in funding of established drugs impede approval of newer agents? Methods: Regulatory agency decisions regarding axitinib, the most recently approved mRCC therapy in the U.S., were reviewed. Reports from the US Food and Drug administration (FDA), the European Medicines Agency (EMA), the pan-Canadian Oncology Drug Review (pCODR), UK's National Institute for Health and Care Excellence (NICE), and the Therapeutic Goods Administration (TGA) of Australia were included. Data abstracted included the date of report publication, basis for determination of clinical efficacy, determination of cost-effectiveness, theme of stakeholder submissions prior to and after the regulatory decision, final decision, and rational for approval/rejection. Results: At the time of analysis, all agency decisions had been finalized. All of the agencies based their assessment of clinical efficacy of primarily on the same phase III clinical trial: the AXIS trial, demonstrating a progression-free survival benefit of axitinib compared to sorafenib (6.7 versus 4.7 months, p<0.001). Cost-effectiveness data was considered by NICE and pCODR, but not the FDA, the EMA, or the TGA. Axitinib was recommended received approval by the FDA, the EMA, and the TGA for use in patients with mRCC who have failed prior treatment with sunitinib or cytokines. pCODR recommended axitinib for funding in the 2^nd line setting only in patients unable to tolerate everolimus. And NICE recommended against the funding of axitinib. Both dissenting organizations cited concerns with the pivotal trial’s control arm, sorafenib, not representing their regional standards of care as primary reasons for restricted access and rejection. Cost considerations were also cited as factors in the rejections. Conclusions: Differing regulatory approvals and funding worldwide are creating regional standards of care that impeding the research, development, and approval of newer agents. Divergent standards of care before and after clinical trials may restrict their external validity and applicability.