Fullerene (nano-C60) and its water-soluble derivatives have several clinical applications including use as a drug carrier to bypass the blood-ocular and blood-brain barriers. However, in vitro and in vivo detection of these nanomaterials is limited by their very low fluorescence quantum yield. The accumulation of fullerene and its derivatives in cells is particularly difficult to measure using standard fluorescence microscopy because their fluorescence is barely detectable in aqueous media. We have developed a time-correlated single-photon counting apparatus with which we were not only able to detect the fluorescence of fullerene and its derivatives in water but could also measure fluorescence temporal decays and determine lifetimes in the range of tens of picoseconds. The compounds studied in this report are C60 (fullerene), the partially hydrogenated hydride C60H36, a monomeric cyclodextrin complexed fullerene [(γ-CyD)2/C60], and C60(OH)24 (fullerol). In addition, we examined the effect of aggregation on photophysical properties and identified a very short lifetime component belonging to the fluorescence decay of monomeric fullerene, which is lost with increasing aggregation. These data will help to design nanoparticles that have the appropriate structural and photophysical properties to ultimately be of use in a clinical setting.