This chapter is an introductory overview of the most commonly used assay methods to estimate the number of viable cells in multi-well plates. This chapter describes assays where data are recorded using a plate-reader; it does not cover assay methods designed for flow cytometry or high content imaging. The assay methods covered include the use of different classes of colorimetric tetrazolium reagents, resazurin reduction and protease substrates generating a fluorescent signal, the luminogenic ATP assay, and a novel real-time assay to monitor live cells for days in culture. The assays described are based on measurement of a marker activity associated with viable cell number. These assays are used for measuring the results of cell proliferation, testing for cytotoxic effects of compounds, and for multiplexing as an internal control to determine viable cell number during other cell-based assays.