Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens which have to interact with mucosa and/or cellular barriers for their life cycle. Even though they both give rise to dramatically different diseases, most of the mechanisms mediating cellular interactions are common to N. meningitidis and N. gonorrhoeae. This suggests that bacterial cell interactions may be essential not only for pathogenesis but also for other aspects of the bacterial life cycle that are common to both N. meningitidis and N. gonorrhoeae. Opacity proteins and pili are two major components identified as transducing signals to host cells, thus leading to cytoskeleton modifications. This manuscript will review the recent developments concerning the mechanisms mediating cellular interactions of pathogenic Neisseria and will tentatively put them into the perspective of pathogenesis and bacterial life cycle.