The American College of Radiology Imaging Network (ACRIN) is the youngest of the National Cancer Institute (NCI) cooperative groups. ACRIN trials are directed towards evaluating the applications of diagnostic imaging and image-guided treatment to cancer. As ACRIN begins its third funding cycle, the organization is increasingly emphasizing several themes: linking imaging surveillance to pre-imaging testing for disease to improve the efficiency of cancer screening; the evaluation of imaging tests as biomarkers for molecular and physiologic processes in cancer; the standardization and validation of imaging tests to predict and monitor response to treatment; improved characterization of the extent and biology of cancer; and the translation of new emerging technologies from first-in-human testing to multicenter trials. ACRIN is poised to pursue its own research agenda, collaborate with other research entities to address key issues in cancer care, and place at the service of the other cooperative groups its electronic infrastructure to improve imaging in therapeutic trials. ACRIN's pursuit of its unique mission as the sole cooperative group directed principally toward diagnosis has made the network an integral part of the cancer research community.