Purpose: The aim of the study was to assess implant survival and complications with implants and prostheses in patients exhibiting a variety of systemic diseases and congenital defects. Materials and Methods: Patients with specific medical conditions are regularly treated at the Department of Prosthodontics, University of Bern, Switzerland. All those who had received implant-prosthodontic treatment during the past 12 years were reexamined for this study. Among these patients the following diseases were observed: cleft lip/palate (n = 8), Down syndrome (n = 3), Sjögren syndrome and scleroderma (n = 2), ectodermal dysplasia (n = 4), developmental retardation (n = 2), chronic leukemia (n = 2), lichen planus (n = 1), cerebral palsy (n = 1), deaf-muteness (n = 1), amyotrophic lateral sclerosis (n = 1). At the time of the treatment the mean age was 55.6 years. ITI implants had been placed according to a standard protocol with local anesthesia, except for one patient in whom full anesthesia was used. One hundred three implants were loaded and supported a total of 34 fixed or removable prostheses. All patients were appointed to a regular maintenance care program. In the context of the present study, all but 1 patient were reexamined clinically. New radiographs were obtained, and the implants and prostheses assessed. Additional information was obtained from regular records in the patients' charts. Results: Three implants were lost in the healing phase, and 1 implant was replaced. Only 1 patient with 4 implants was lost from the study (she had passed away). The survival rate of the loaded implants was 100%. In 1 patient, peri-implant bony defects were detected around all 3 intraforaminal implants. The prosthetic plan was maintained in all patients, and they continued to wear the originally planned type of prosthesis. Complications included insufficient hygiene, soft tissue hyperplasia, extraction of remaining teeth, and minor maintenance or repair of the prostheses. Conclusions: So far, the mostly unknown implications and possible risks for the process of osseointegration and long-term maintenance in patients with such rare diseases and defects has resulted in a rather restricted application of implants. However, from the present results, it appears that implants can successfully be placed and maintained. This is ascribed in part to a strict maintenance care program provided by the caregivers and to a high compliance of the patients who participated in this program to perform good oral hygiene.