The novel optical, electrical, and magnetic properties of ultra-small inorganic nanoparticles make them very attractive in diverse applications in the fields of health, clean and renewable energy, and environmental sustainability. This article comprehensively summarizes state-of-the-art fluorescence imaging using ultra-small nanoparticles as probes, including quantum dots, metal nanoclusters, carbon nanomaterials, up-conversion, and silicon nanomaterials.