Moraxella catarrhalis is a Gram-negative bacterium, exclusively present in humans and a leading causative agent of otitis media (OM) in children. Most children (80 %) experience at least one episode of OM by their third birthday and half suffer multiple episodes of infection. Over the last 10 years, increased evidence suggests that M. cat possesses multiple virulence factors which can be carried through biologically active outer membrane vesicles (OMVs) that are themselves able to activate host-immune responses. It has also been noted that multiple toll-like receptors are responsible for M. cat recognition. This review is intended to summarize the key findings and progress in recent years of the molecular mechanisms of M. cat-induced otitis media with particular emphasis on adhesion, invasion, and activation of the host immune system, biofilm formation, and vaccine development.