The metaphase to anaphase transition is a point of no return; the duplicated sister chromatids segregate to the future daughter cells, and any mistake in this process may be deleterious to both progeny. At the heart of this process lies the anaphase inhibitor, which must be degraded in order for this transition to take place. The degradation of the anaphase inhibitor occurs via the ubiquitin-degradation pathway, and it involves the activity of the cyclosome/anaphase promoting complex (APC). The fidelity of the metaphase to anaphase transition is ensured by several different regulatory mechanisms that modulate the activity of the cyclosome/APC. Great advancements have been made in this field in the past few years, but many questions still remain to be answered.