A series of prospective studies started in the mid-1980s at the University of Toronto have provided evidence of the efficacy and effectiveness of implants in the treatment of the fully and partially edentulous patients. These studies have focused primarily on treatment outcomes at the surgical and prosthodontic levels, with an overall failure rate of 7.7% over a 20-year period. Because a considerable proportion of these failures (4.2%) occurred before insertion of the prosthesis, and because osseointegration is essentially a wound-healing process, factors that interfere with healing, including systemic conditions, may contribute to implant failure. This paper reviews studies on the impact of selected systemic conditions, including osteoporosis, cardiovascular diseases, diabetes mellitus, and hypothyroidism, as well as smoking behaviour, on the success or survival of oral implants in patients treated in the Implant Prosthodontic Unit at the University of Toronto.