We compare frequency-and time-domain formulations of deep-tissue fluorescence imaging of turbid media. Simulations are used to show that time-domain fluorescence tomography, implemented via the asymptotic lifetime-based approach, offers a significantly better separability of multiple lifetime targets than a frequency-domain approach. We also demonstrate experimentally, using complex-shaped phantoms, the advantages of the asymptotic time-domain approach over a Fourier-based approach for analyzing time-domain fluorescence data.