Time-of-flight (TOF) PET was initially introduced in the early days of PET. The TOF PET scanners developed in the 1980s had limited sensitivity and spatial resolution, were operated in 2-dimensional mode with septa, and used analytic image reconstruction methods. The current generation of TOF PET scanners has the highest sensitivity and spatial resolution ever achieved in commercial whole-body PET, is operated in fully-3-dimensional mode, and uses iterative reconstruction with full system modeling. Previously, it was shown that TOF provides a gain in image signal-to-noise ratio that is proportional to the square root of the object size divided by the system timing resolution. With oncologic studies being the primary application of PET, more recent work has shown that in modern TOF PET scanners there is an improved tradeoff between lesion contrast, image noise, and total imaging time, leading to a combination of improved lesion detectability, reduced scan time or injected dose, and more accurate and precise lesion uptake measurement. Because the benefit of TOF PET is also higher for heavier patients, clinical performance is more uniform over all patient sizes.