Multi-shot echo planar imaging (msEPI) is a promising approach to achieve high in-plane resolution with high sampling efficiency and low T2* blurring. However, due to the geometric distortion, shot-to-shot phase variations and potential subject motion, msEPI continues to be a challenge in MRI. In this work, we introduce acquisition and reconstruction strategies for robust, high-quality msEPI without phase navigators. We propose Blip Up-Down Acquisition (BUDA) using interleaved blip-up and -down phase encoding, and incorporate B0 forward-modeling into Hankel structured low-rank model to enable distortion-and navigator-free msEPI. We improve the acquisition efficiency and reconstruction quality by incorporating simultaneous multi-slice acquisition and virtual-coil reconstruction into the BUDA technique. We further combine BUDA with the novel RF-encoded gSlider acquisition, dubbed "BUDA-gSlider", to achieve rapid high isotropicresolution MRI. Deploying BUDA-gSlider with model-based reconstruction allows for distortion-free whole-brain 1mm isotropic T2 mapping in ~1 minute. It also provides whole-brain 1mm isotropic diffusion imaging with high geometric fidelity and SNR efficiency. We finally incorporate sinusoidal "wave" gradients during the EPI readout to better use coil sensitivity encoding with controlled aliasing.Recently, Hankel structured low-rank constrained PI approaches 8-12 were proposed to enable navigator-free msEPI acquisition with higher in-plane acceleration to minimize geometric distortion. However, achieving adequate image quality at higher acceleration necessitates a larger number of shots (e.g., Rinplane=8 with 4-shots), thereby limiting the efficiency of such acquisitions. In previous work 13-15 , we incorporated virtual coil (VC) concept 16 and simultaneous multi-slice (SMS) acquisition 17,18 into structured low-rank model and deep learning-based reconstructions to further accelerate msEPI. Similar works were reported by other groups 19,20 .In this study, we propose an efficient Blip Up-Down Acquisition (BUDA), where a 2-shot EPI sampling was performed with interleaved blip-up and -down acquisitions, and then combined with B0 forward-modeling and structured low-rank reconstruction to yield distortion-free images. With BUDA, the required number of shots was reduced to two, which improved the sampling efficiency of msEPI. We demonstrate its extension to the VC concept through structured low-rank reconstruction and obtain high-quality images from a partial Fourier 75% acquisition. We further combine BUDA with a * BBILGIC@mgh.harvard.edu