The activity of the reporter protein is typically assayed by photometry, colorimetry or fluorometry. Recently, detection systems based on bioluminescence, chemiluminescence and fluorescence have become widely used because of their signal detection sensitivity and ease of use. Improved detection equipment, such as charge-coupled device (CCD) cameras, has also enabled the development of convenient reporter assay systems for drug screening. There are two major types of reporters, i.e., intracellular and extracellular reporters. Intracellular reporter gene products are expressed and retained inside the cells. On the other hand, extracellular reporter genes encode proteins that are secreted into the medium of cultured cells or the blood stream in animals. Some intra-and extracellular reporter gene assays may detect the reporter protein's activity without killing the cells or animals in which the assay is performed. This allows time-course experimentation by sampling of the medium of cultured cells, or the blood plasma of research subjects. As such, report bioassays are potentially suitable for high throughput screening (HTS) of small molecule drug candidates. Bioassays are used to determine the concentration or biological activity of molecules such as hormones, growth factors, and enzymes. Moreover, they can be used for measuring the effects of candidate drugs on an organism, cultured cells, or recombinant receptors by comparison to gold standard molecules with known target activity. The present review provides an overview of the basic properties, efficacies and limitations of protein reporter assays, with an emphasis on their application as bioassays for drug screening.