The French-style organization in the field of rare diseases allows a close contact between reference centres and regional pharmacovigilance centres thanks to their implementation within the French university hospital. This collaboration leads to highlight more and more drug-induced rare diseases. Through several historical examples (eosinophilia-myalgia syndrome due to L-tryptophan, type 1 narcolepsy with H1N1 pandemic influenza vaccine, capillary leak syndrome, acquired von Willebrand syndrome), it remains clear that pharmacovigilance is the cornerstone of the alert system. Clinicians from the rare disease reference centres can easily report adverse drug reactions (ADRs) to pharmacologists from their regional pharmacovigilance centre. Through experience, collaboration between countries, large database, and sometimes pharmacoepidemiological studies, an alert can then be raised. This collaboration underlines also similarities between the two disciplines, through the frequency of ADRs and diseases, the difficulty of the diagnosis in front of scarce data, and through the unusual worsening symptoms. Patients and associations of patients play also a proactive role as research partners at different steps, to quantify and qualify symptoms and ADRs, and also to develop orphan drugs. These several collaborations are a precious tool to improve patients’ outcomes. These close contacts between the different actors are important to make earlier diagnosis of rare diseases and severe ADRs. Rare disease does not have to mean overlooked diseases.