The outcome of treating an infection with an antibiotic in a human being is not only a function of which antibiotic is chosen but is also dependant on many host variables (eg, age, immune function, etc). Vancomycin MICs tend to “creep” upward with recurrent exposure to the drug. Patients who require multiple rounds of vancomycin tend to be sicker and suffer from other underlying conditions such as end-stage renal disease, which could easily explain the observed mortality differences. Although vancomycin is certainly not the most effective antistaphylococcal antibiotic, it is relatively inexpensive and well-studied. Before we routinely recommend the use of alternative therapies, which may cost > 1,000% of vancomycin’s acquisition cost, for susceptible organisms, we should demand evidence that (1) any failure is truly due to antibiotic issues and not simply a function of host factors and (2) that other drugs are truly superior in such patients. While not cheap, it should be possible to design a study of patients with MRSA bacteremia or pneumonia with MICs ≥1 μg/mL and randomize them to continued vancomycin vs switching to comparator antibiotics. If it is indeed a vancomycin issue, comparator drugs should be able to prove their superiority and thereby validate the excess cost associated with these medications. If the higher failure rates and increased mortality are due to host issues, however, changing the antibiotic will not have the desired effect. Recommendations to change a treatment paradigm should not be based on observational studies, animal studies, and pharmacokinetic modeling when randomized trials are feasible. I actually believe that other drugs should be able to outperform vancomycin, but until companies making these drugs actually complete relevant studies, we should be careful to preempt a new standard of care, as is recommended by the authors of this study.