e-Science encompasses computational science and adds the new dimension of the routine sharing of distributed computational, data, instruments and specialist resources. This paper describes the £120M UK ‘e-Science’ initiative, focusing on the ‘Core Programme’. The majority of the funding is for large-scale e-Science pilot projects in many areas of science and engineering. The pilot e-Science projects that have been announced to date are briefly described. These projects span a range of disciplines from particle physics and astronomy to engineering and healthcare, and illustrate the breadth of the UK e-Science Programme. The requirements of these projects and the recent directions in developments of open source middleware have provided direction for the roadmap of development within the Core Programme. The middleware infrastructure needed to support e-Science projects must permit routine the sharing of any remote resources as well as supporting effective collaboration between groups of scientists. Such an infrastructure is commonly referred to as the Grid. The focus of the paper is on the Core Programme that has been created in order to advance the development of robust and generic Grid middleware in collaboration with industry. The key elements of the Core Programme will be outlined including details of a UK e-Science Grid.