The principle advantages of an ATP assay include that it is currently the most rapid and sensitive HTS method available for assessing viability. For instance, as few as 10 cells can be detected in limiting dilution series of eukaryotic cells within 10 minutes (Fig. 2) . The assays also benefit from relatively high signal to background ratios, which enable routine miniaturization into 1536 well formats [36, 37] . Furthermore, luminescence signals are not encumbered by intrinsically fluorescent test compounds [38] . Despite an abundance of advantages for HTS implementation, ATP assays also carry liabilities. Because the ATPdependent luciferase reaction rate is susceptible to temperature flux, equilibration to constant room temperature is required to minimize thermal gradients created by plate well position (edge-effects). Also, like other metabolic assay chemistries used to measure viability, ATP is (rarely) subject to positive or negative modulation by test reagents independent of loss of viability leading to misleading data [39, 40] . Lastly, all commercial formulations of ATP-detection chemistries are susceptible to luciferase inhibition to various degrees by small molecule compounds. Recent evidence suggests that specific formulations may greatly minimize the extent of this inhibition [41] .