The assessment of kidney function is a cornerstone in the clinical management and health of the patient. Although the kidneys perform many physiologic functions and are essential for maintaining homeostasis, kidney function is typically evaluated, quantitated, and understood using the glomerular filtration rate (GFR). Although GFR can be directly measured using a variety of externally administered glomerular filtration markers, in general practice, the GFR is usually estimated (eGFR) using endogenous markers that are cleared primarily by kidney filtration. Common situations exist where the GFR needs to be measured (mGFR) in order to proceed with care. This manuscript will review laboratory challenges in the assessment of GFR. Key points to consider when implementing a mGFR testing protocol are the following: marker selection, clearance methodology (urinary vs solely plasma measurements of filtration marker), sample collection, number of samples to collect, staff required, and analytical measurement technology for the filtration marker selected. We suggest those wanting to implement mGFR testing examine site-specific institutional resources along with patient population and proceed with the approaches best suited for their clinical needs and laboratory resources available.