Past editions of the American Association of State Highway and Transportation Officials (AASHTO) Guide for Design of Pavement Structures have served well for several decades; nevertheless, many serious limitations exist for their continued use as the nation's primary pavement design procedures. Researchers are now incorporating the latest advances in pavement design into the new Mechanistic-Empirical Pavement Design Guide (MEPDG), developed under the National Cooperative Highway Research Program (NCHRP) 1-37A project and adopted and published by AASHTO. The MEPDG procedure offers several dramatic improvements over the current pavement design guide and presents a new paradigm in the way pavement design is performed. However, MEPDG is substantially more complex than the AASHTO Design Guide by considering the input parameters that influence pavement performance, including traffic, climate, pavement structure and material properties, and applying the principles of engineering mechanics to predict critical pavement responses. It requires significantly more input from the designer. Some of the required data are either not tracked previously or are stored in locations not familiar to designers, and many data sets need to be preprocessed for use in the MEPDG. As a result, tremendous research work has been conducted and still more challenges need to be tackled both in federal and state levels for the full implementation of MEPDG. This paper, for the first time, provides a comprehensive bird's eye view for the MEPDG procedure, including the evolvement of the design methodology, an overview of the design philosophy and its components, the research conducted during the development, improvement, and implementation phases, and the challenges remained and future developments directions. It is anticipated that the efforts in this paper aid in enhancing the mechanistic-empirical based pavement design for future continuous improvement to keep up with changes in trucking, materials, construction, design concepts, computers, and so on.