This article addresses clinical trials in oncology that require independent data monitoring committees (IDMCs). The word “independent” emphasizes that members of these committees are neither part of the sponsor organization nor trial investigators. Typically, trials in oncology with IDMCs are multicenter, large, and of long-duration. The usual outcome is death, progression-free survival (PFS), or sometimes response rate. Some are smaller trials where outcomes may be tumor size or biomarker data. Ideally, controlled clinical trials are double-masked; however, in oncology many such trials are necessarily open-label or single masked. Some trials with IDMCs may be single-arm studies.