The need to screen more compounds in a given time is serving as a driving force for HTS laboratories to use high-density multiwell plates (e.g., 1536-or 3456-well plates) as well as liquid handling and plate reader formats that can support them. The 1536well plate has become the industry workhorse and the feasibility of cell-based assays in these plates has been reported in the literature (Table 9.1). Two key observations can be made from the information presented in Table 9.1. First, the popularity of receptors and enzymes as targets is consistent with the two being the most common target classes for current drug therapies (Drews, 2000). Kinases have emerged as one of the most important target classes for drug discovery and development; this is because, as with GPCR targets, of their crucial role in cellular signaling (Cohen, 2002). Second, the most prevalent readout signal types are luminescence and uorescence. Additional con rmation of this can be found from recent surveys of HTS Laboratory Directors (HighTech Business Decisions, 2007), where the top two readout technologies for both 2006 and 2008 surveys were time-resolved uorescence resonance energy transfer (TR-FRET) and glow luminescence. In the same survey, the top planned purchase detection technology was label-free.