Various approaches for treating the periodontal condition associated with Papillon-Lefèvre syndrome (PLS) have been reported. These include oral hygiene instruction, use of mouth rinses, frequent debridement, multiple antibiotic regimens, periodontal surgery, extraction of hopeless teeth, and extraction of all primary teeth. The objective of this paper is to review the literature on the different treatment approaches of patients with PLS and to illustrate the importance of early diagnosis as well as treatment in long-term maintenance of oral health. Because PLS is rare, most publications are case reports, and very few document long-term successful treatment of the periodontal condition. Several treatment approaches are summarized in this paper with the long-term reports. The importance of early diagnosis is highlighted. The recommendation is that young patients with skin lesions and severe periodontal destruction together with premature loss of teeth should be referred to a periodontist as early as possible. This should prevent or delay tooth loss and enhance early replacement of missing teeth for preservation of function and esthetics. In conclusion, successful periodontal management of PLS patients remains challenging. However, as our understanding of the etiological factors increases, it is hoped that successful treatment strategies will be developed.