By the end of the nineties, new immunomodulatory options impacting on the determinants of many immune-mediated diseases became available. These drugs were also called biologicals. Their use was associated with a significant improvement in the management of the patients and on their clinical evolution over time. On the other hand, their use was found to be also associated with an over-risk of infectious complications, in particular of viral origin, even though the savings of other at-risk treatments (e.g. corticosteroids or cyclophosphamide) allowed by these new therapies could have contributed to reduce it. These viral infections may be linked to an increased susceptibility to new infections because of impaired immunity and/or lower responsiveness to vaccination, to a higher risk of reactivation of latent infections, and to a higher severity than observed in the general population. Viruses mostly involved are respiratory (influenza, RSV, and SARS-CoV2), Varicella-Zoster, hepatitis B, or JC viruses, in particular. The viral risk depends not only on the type of biologicals, but also on the underlying disease, the associated comorbidities, the associated treatments, the epidemiological environment, and the individual and collective immunity. At an individual level, prevention and management of the infectious risk are of utmost importance in the global management of patients on biologicals.