ICP0 protein of herpes simplex virus type 1 (HSV-1) constitutes one of the major sub jects of studies in the field of herpesviruses. Its biological properties in relation with the ubiquitination of proteins, the induction of the degradation of numerous substrates by the proteasome, as well as its multiple interactions with different cellular components, contribute to its fundamental role in the infection process. These last few years the E3 ubiquitin ligase activity of ICP0 has been formally demonstrated. In this review, I will do an overview of what has been published on this activity, and I will briefly come back on some of the key aspects of the infectious process controlled by ICP0.