The technical challenges and obstacles to scaling-up of fuel cells are diverse, including such issues as water, heat, materials, catalyst, and flow fields because of multiple chemical and physical interactions at the atomic level and stack system level. The current results and data, even assumptions and guidelines are separated, inconsistent or unconnected. The unconnected data is partly the result of different disciplines. This paper is a first attempt toward understanding and analyzing the massive but spread-out work, which has been done and reported in the literature on fuel cell performance, reliability and durability. In this, we analyze the procedure of fuel cell research and development, and break down the barriers of scaling-up into four different stages: component, individual cell, stack and system control. We find that there are three different operating windows at each stage of the components, individual cells, and stack. While the operating window of components (e.g., membrane) are defined as ranges of temperature and relative humidity (RH), the operating window of a cell must include channel velocity and pressure drop within the cell. The operating window of a stack becomes narrower than that of its individual cells due to uneven flow distribution and load change. We have also found that there are knowledge gaps in the different stages of development. A solution for fuel cell scaling-up and a connection can be built among the components, cells, stack, process and system control through the operating windows and flow fields. The concepts of the three operating windows and flow field designs can build a connection among properties of the material and structures of components (e.g., wettability, porosity, and hydrophobicity), flow field, cells and performance of a stack and macro operation conditions (e.g., pressure, humidity and flow rates). This clarifies key ambiguities and converges our future directions on how to bridge different stages or disciplines of research and development. These can provide a new insight for future research to address the key issues of durability and reliability that remain unsolved.