Optical molecular imaging is the best approach to monitor multiple molecule events and cell functions simultaneously in complex organisms. Since immune system provides defense, surveillance and self-stabilizing functions for lives, the major challenge for researchers is to consider immune system as a system. Immunophotonics refers to in vivo immune optical imaging (Immuno-Optimaging) and immune photonic therapy (Immuno-Phototherapy) based on the principle and method of photonics. The combination of in vivo optical imaging with high spatio-temporal resolution, such as multi-photon excitation microscopy and photoacoustic tomography, and intravital long-term labeling method based on fluorescent proteins, makes optical molecule imaging be the main force of guiding immunologists to embrace the era of systematization and visualization. Here, based on the characteristics and needs of immunology, we introduce the latest development of in vivo optical molecular imaging and molecular probes, review the applications of those techniques and methods in immunology research, and further discuss the prospect of the future development of immunophotonics.