Clinicians have a range of options for treating patients with disease states that require the use of immunoglobulin (Ig). Traditionally, intravenous immunoglobulin (IVIG) administration has provided effective therapy for a variety of disease states. More recently, subcutaneous immunoglobulin (SCIG) administration has become available for patients with primary immunodeficiencies and chronic inflammatory demyelinating polyneuropathy (CIDP). Ig is used as replacement therapy in patients with primary or secondary immunodeficiencies and has been shown to reduce morbidity due to bacterial infections associated with antibody deficiency. The mechanism of action for use of Ig in the treatment of autoimmune disorders is complex and partially understood, but immunomodulatory effects have been suggested in CIDP and multifocal motor neuropathy. The available IVIG and SCIG products differ in their pharmaceutical properties (eg, pH, osmolality, IgA content, sodium content, and stabilizer), which can affect safety and tolerability in some patients. The pharmacokinetics of Ig also differ based on the route of administration. With IVIG administration every 3 or 4 weeks, peak concentrations are greater and trough concentrations are lower, which can increase the propensity of systemic adverse effects (AEs) and impact tolerability of therapy. SCIG infusions are typically administered more frequently (ie, biweekly, weekly, and even daily based on patient need), resulting in steady state concentrations with fewer fluctuations in Ig plasma levels. The route of administration plays a major role in the types of AEs seen in patients receiving Ig therapy, with systemic AEs associated with IV administration and local reactions more commonly seen with SC administration. By understanding the differences in IVIG and SCIG products, which are not interchangeable, and the patient characteristics that guide product selection, clinicians and managed care providers can better serve patients with immunodeficiency disorders and other disease states.