The principle behind two-photon-excited fluorescence microscopy is simple: In the presence of laser pulses, molecules simultaneously can absorb two or more photons at longer wavelengths with the same effect as absorbing one photon at a much shorter wavelength. Unfortunately for science, most known organic molecules have a relatively small photon absorption cross section, and the criteria for designing materials with a higher absorption threshold has remained a mystery. That is until now. A collection of researchers from Cornell University in Ithaca, N.Y., the Center for Research on Molecular Electronics and Photonics at the University of Mons-Hainaut in Mons, Belgium, the Jet Propulsion Laboratory and the California Institute of Technology, both in Pasadena, Calif., have reported on design strategies and structure-property studies for two-photon absorption. Using this new information, researchers hope to synthesize fluorescent molecules with an unprecedented brightness in two-photon fluorescence imaging.