The ability to label individual molecules inside of living cells with fluorescent probes has revolutionized our understanding of basic cell biology and opened new opportunities to bioengineer living cells. Laser scanning confocal microscopy has proved to be a powerful and versatile technique for studying fluorescent molecules in cells. Rice University recognized the importance of this technique, and purchased a Zeiss LSM 410 confocal microscope in 1993. This microscope has supported numerous research projects in cell biology and bioengineering. However, there are serious limitations in the current technology, including limited ability to resolve molecules with overlapping emission spectra and the damage to cells that occurs with laser excitation. The importance and magnitude of these issues led Carl Zeiss, Inc. to expend a significant amount of time and resources to develop a user-friendly system that can overcome these problems. Zeiss recently integrated powerful new technologies, including novel algorithms for resolving overlapping emission spectra and the ability to use multi-photon laser excitation, into their new confocal microscope. The new system is called the 510 LSM META/NLO.