Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application. Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies. Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5-8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%-276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%-92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results. Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection compared with respiratory gating and no motion correction while reducing radiation dose. In vivo primate and rabbit studies confirmed the improvement in PET image quality and provide the rationale for evaluation in simultaneous whole-body PET/MRI clinical studies.