Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest.J.B. and S.E.B. are supported by the EPSRCCRUK Cancer Imaging Centre in Cambridge and Manchester (No. C197/A16465); CRUK (Nos. C14303/A17197 and C47594/A16267); and the European Union’s Seventh Framework Programme (No. FP7/2007-2013) under Grant Agreement No. FP7-PEOPLE-2013-CIG-630729. J.Y. is partly supported by Duke MEDx Basic Research Grant. J.L. acknowledges the support of ERC Starting Grant No. 281356
