There is an increasing need for versatile yet sensitive labels, posed by the demands for low detection in bioanalysis. Bioluminescent proteins have many desirable characteristics, including the ability to be detected at extremely low concentrations; no background interference from autofluorescent compounds present in samples; and compatibility with many miniaturized platforms, such as lab-on-a-chip and lab-on-a-CD systems. Bioluminescent proteins have found a plethora of analytical applications in intracellular monitoring, genetic regulation and detection, immuno- and binding assays, and whole-cell biosensors, among others. As new bioluminescent organisms are discovered and new bioluminescence proteins are characterized, use of these proteins will continue to dramatically improve our understanding of molecular and cellular events, as well as their applications for detection of environmental and biomedical samples.