Advances in networking technologies will soon make it possible to use the global information infrastructure in a qualitatively different way—as a computational as well as an information resource. As described in the recent book The Grid: Blueprint for a New Computing Infrastructure, this Grid will connect the nation’s computers, databases, instruments, and people in a seamless web of computing and distributed intelligence, which can be used in an on-demand fashion as a problem-solving resource in many fields of human endeavor—and, in particular, science and engineering. The availability of grid resources will give rise to dramatically new classes of applications, in which computing resources are no longer localized but, rather, distributed, heterogeneous, and dynamic; computation is increasingly sophisticated and multidisciplinary; and computation is integrated into our daily lives and, hence, subject to stricter time constraints than at present. The impact of these new applications will be pervasive, ranging from new systems for scientific inquiry, through computing support for crisis management, to the use of ambient computing to enhance personal mobile computing environments. To realize this vision, significant scientific and technical obstacles must be overcome. Principal among these is usability. The goal of the Grid Application Development Software (GrADS) project is to simplify distributed heterogeneous computing in the same way that the World Wide Web simplified information sharing over the Internet. To that end, the project is exploring the scientific and technical problems that must be solved to make it easier for ordinary scientific users to develop, execute, and tune applications on the Grid. In this paper, the authors describe the vision and strategies underlying the GrADS project, including the base software architecture for grid execution and performance monitoring, strategies and tools for construction of applications from libraries of grid-aware components, and development of innovative new science and engineering applications that can exploit these new technologies to run effectively in grid environments.