The challenges of appropriate drug dosing in patients with renal failure requiring renal replacement therapy (RRT) have been exacerbated by recent trends in both RRT technology and practices. Nearly all these changes have resulted in augmented drug clearance, making most existing RRT drug dosing recommendations obsolete. Many barriers exist to conducting research to update our knowledge of appropriate drug dosing in the context of contemporary RRT. Recommendations on how this research could be conducted, including the use of in vitro techniques, are offered here.