Bovine respiratory disease (BRD) inflicts significant losses in cattle farming worldwide and is caused by the co-occurrence of various infectious agents which is often compounded by environmental factors. It is well known that microorganisms of the Mollicutes class are responsible for respiratory disorders in cattle, including BRD. This review highlights the current role of these microorganisms, in particular Mycoplasma bovis and Mycoplasma dispar, in the etiology of this disease complex, which has recently shifted toward a primary or predominant cause of the disease.