A benchmark review on how specific nutrients or adverse nutritional states impact the components of the IGF (Insulin-like Growth Factor) system and affect human health and disease. The authors describe the fundamentals of the IGF system, explain its basic mechanisms of action, illuminate its essential role in physical development across the life span, and highlight the link between normal and abnormal cellular growth resulting in tumor formation. They also fully examine the clinical aspects of nutrition and IGF, from pre- and postnatal development through old age, in the maintenance of normal metabolism, bone, and muscle health, and their role in pathological states. Special attention is given to critical illness, diabetes, gastrointestinal diseases, kidney failure, endocrine dysfunctions, cardiovascular disease, neurological disorders, and cancer, as well as to their potential for IGF therapy.