Distinctive risk factors for disease are identifiable throughout life stages of large- and giant-breed dogs. From weaning to maturity, improper nutrition is linked to developmental skeletal diseases. As large dogs mature, skeletal diseases and obesity can lead to osteoarthritis. These dogs are difficult to manage when orthopedic or osteoarthritic disease affects mobility and quality of life, thereby increasing the risk of early death. Gastric dilatation and volvulus is another disease that is leading cause of death in large- and giant-breed dogs. Management of health, including proper nutrition, exercise, and weight control, provides the best opportunity for successful aging of large- and giant-breed dogs.