Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has become one of the leading indications for liver transplant. Despite intensive investigations, there are currently no FDA approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing non-invasive, objective and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) as a non-invasive, quantitative, and accurate measure of liver fat content to assess treatment response in early-phase of NASH trials. In this review, we will discuss the role and utility, including potential sample-size reduction, of using MRI-PDFF as a quantitative and non-invasive imaging-based biomarker in early-phase NASH trials. This article is protected by copyright. All rights reserved.