In his daily practice, the orthodontist is regularly asked to treat patients with one or more missing teeth. Considering their functional and esthetic specificities, and the relatively high frequency of agenesia, our interest was to focus on the permanent lateral upper incisors. Our study, based on an orthodontic population including 1000 patients, shows that about 7.8% of these patients present agenesis of at least one permanent tooth (out of which 3.6% are agenesis of the upper lateral incisor). Treatment options for these cases are multiple with several decisional factors to consider: the solutions often lead to compromises, and require a multidisciplinary coordination. Therefore, the purpose of this article, was to describe the prevalence of these agenesia based on a retrospective study, and to present two clinical cases: the first case is a bilateral agenesis of the maxillary lateral incisors treated with space opening in order to place two implant-supported restorations. The second case is an agenesis of tooth 12 treated with space reopening and the placement of a cantilever bridge. These clinical cases are presented to illustrate the multidisciplinary approach involving orthodontics, prosthodontics, and periodontology, in order to achieve the most esthetic and functional results possible.