A review of photodetectors for optical detection in biological applications is presented. The intent is to provide an overview of the performance metrics and trade-offs among popular photodetectors in order to facilitate an easier match among the photodetector, biological stimulus, and optical pathway. The characteristics and nonidealities of fluorescent and phosphorescent reporters, and the properties of optical components such as filters, lenses, and light sources, are reviewed. By accounting for sources of noise in these components, it is shown how to determine metrics for the optical system that can then be converted to photodetector metrics. Defined photodetector metrics include the quantum efficiency, responsivity, noise-equivalent power, detectivity, gain, dark current, response time, and noise spectrum. The operating principles and performance trade-offs of photodetectors are reviewed, and emphasis is placed on photodetectors for integrated compact systems. Top commercial candidates for photodetectors for detecting light emitted from reporters are the photomultiplier tube, avalanche photodiode, and charge-coupled device. Focus is placed on new developments in complementary metal-oxide-semiconductor structures that can provide low-cost, low-power, and low-voltage alternatives to traditional approaches to biological imaging. Reviewed device structures are presented in the context of supporting the development of laboratory-based instruments and compact fully-integrated systems.