The microbiome can trigger and maintain immune-mediated diseases and is associated with the severity and prognosis of idiopathic pulmonary fibrosis, which is the prototype of interstitial lung diseases (ILDs). The latter can be a major cause of morbidity and mortality in patients with connective-tissue diseases (CTD). In the present review, we discuss the current evidence regarding microbiome in CTD-ILD and pulmonary vasculitis. In patients with rheumatoid arthritis (RA) the BAL microbiota is significantly less diverse and abundant, compared to healthy controls. These changes are associated with disease severity. In systemic sclerosis (SSc), gastrointestinal (GI)-dysbiosis is associated with ILD. Butyrate acid administration as a means of restoration of GI-microbiota has reduced the degree of lung fibrosis in animal models. Although related studies are scarce for SLE and Sjögren's syndrome, studies of the gut, oral and ocular microbiome provide insights into the pathogenesis of these diseases. In ANCA-associated vasculitis, disease severity and relapses have been associated with disturbed nasal mucosa microbiota, with immunosuppressive treatment restoring the microbiome changes. The results of these studies suggest however no causal relation. More studies of the lung microbiome in CTD-ILDs are urgently needed, to provide a better understanding of the pathogenesis of these diseases.