Contrast-detail analysis is used to evaluate the imaging performance of diffuse optical fluorescence tomography (DOFT), characterizing spatial resolution limits, signal-to-noise limits, and the trade-off between object contrast and size. Reconstructed images of fluorescence yield from simulated noisy data were used to determine the contrast-to-noise ratio (CNR). A threshold of was used to approximate a lowest acceptable noise level in the image, as a surrogate measure for human detection of objects. For objects inside the edge of a simulated tissue region, the smallest diameter that met this criteria was approximately , regardless of contrast level, and test field diameter had little impact on this limit. Object depth had substantial impact on object CNR, leading to a limit of for objects near the center of a test field and for an test field. Similarly, large objects near the edge of both test fields required a minimum contrast of 50% to achieve acceptable image CNR. The minimum contrast for large, centered objects ranged between 50% and 100%. Contrast-detail analysis using human detection of lower contrast limits provides fundamentally important information about the performance of reconstruction algorithms, and can be used to compare imaging performance of different systems.