Spin-off firms may be seen as a key mechanism for the external transmission of knowledge developed at universities. The proliferation of academic spin-offs in recent years has led universities to develop specific rules for the regulation and management of the spin-off process. This paper draws on the Italian experience. More than fifty Italian universities issued spin-off regulations between 2001 and 2008. The author looks at the reasons why Italian universities have decided to issue these specific regulations to control the research spin-off phenomenon, assesses the similarities and differences between the regulations of various universities and examines whether and to what extent the regulations are useful. (Contains 4 tables and 2 figures.)