The spindle checkpoint delays anaphase onset in the presence of defective kinetochore-microtubule attachments. Such delays can last for just a few minutes or several hours, but very shortly after all chromosomes achieve bi-orientation, a remarkably synchronous anaphase ensues. We are beginning to understand the pathways involved in silencing spindle checkpoint signals and subsequent activation of the anaphase-promoting complex. Here, we review recent advances made in our understanding of the molecular mechanisms regulating this critical cell cycle transition.