During mitosis, cohesin holds the replicated chromosomes together until, at anaphase, its proteolytic cleavage by separase ensures that cell division produces two identical daughter cells. Separase activity is controlled in higher eukaryotes by the inhibitor securin, but cyclin B1 also binds to phosphorylated separase. On p. 3325, Andrew Holland and Stephen Taylor provide new insights into the role of this interaction by reporting that cyclin-B1-mediated inhibition of excess separase is essential for timely chromosome disjunction. They show first that mitosis-specific phosphorylation of human separase on S1126 is required to initiate but not maintain cyclin B1 binding. Then they show that overexpression of a non-phosphorylatable form of separase (S1126A) induces premature loss of sister chromatid cohesion in human cells: securin-mediated inhibition of separase fails because of the overabundance of separase; cyclin-B1-mediated inhibition fails because separase phosphorylation is prevented. Surprisingly, however, chromatid cohesion in these cells is normal in early mitosis. Thus, suggest the authors, yet another inhibition mechanism must prevent cleavage of cohesin by separase during early mitosis.