This chapter describes the Cancer Biomedical Informatics Grid (caBIG®) project, a collaboration among the National Cancer Institute (NCI) and numerous discovery organizations, mostly NCI-designated cancer centers. The rationale for the caBIG® project opens the review, followed by description and analysis of the pilot phase (2004–2007). Changes in caBIG® as it transitions to an enterprise phase are evaluated. The chapter concludes with a review of important papers that either describe caBIG® components or are based on the initiative.