Exogenous antibody therapy to protect patients against infections and toxins is over 100 years old, yet progress continues to be made in the manufacture, administration and application of this type of immunotherapy, known as therapeutic human immunoglobulin. For the majority of patients with primary immunodeficiencies, immunoglobulin replacement is the only life-saving therapy and treatment is life-long, since the vast majority of primary immunodeficiency patients have primary antibody failure. Successful treatment depends on multiple factors: the availability of products, the type of immunodeficiency and any comorbidities of the individual patient. Essential components include long-term follow-up, regular monitoring and a close relationship between the patient and the multidisciplinary clinical immunology team. In this article, we describe the current immunoglobulin products and the types of adverse reactions. We provide evidence for clinical decision-making regarding dosing, route of administration and location of therapy, highlighting current ‘best practice’ recommendations.