Combination syndrome (CS) is a dental condition that is commonly seen in patients with a completely edentulous maxilla and partially edentulous mandible with preserved anterior teeth. This syndrome consists of severe anterior maxillary resorption combined with hypertrophic and atrophic changes in different quadrants of maxilla and mandible. This makes it a challenging condition in dentistry that requires significant experience along with advanced restorative and surgical skills. The causes of maxillary bone resorption and ways to correct it are discussed in this article. Conventional treatment with full upper and partial lower dentures for the CS patients is not always adequate or satisfying for patients and it often requires multiple remakes due to continuing bone resorption. Dental implant rehabilitation challenges conventional treatment with bone-anchoring techniques to provide improved retention and stability for implant-retained and supported prostheses. This article presents a successful implant treatment of the partially edentulous maxilla in CS patient. The author proposes a new classification of the combination syndrome that includes a multitude of CS cases with partial and complete maxillary and mandibular edentulism. The necessity of a multi-disciplinary approach for early prevention and treatment of this complex condition is emphasized.