Purpose A review of the different formulations of intravenous immunoglobulin (IVIG) replacement therapy for primary immunodeficiency and other severe diseases, focusing on the comparative efficacy, safety, and tolerability of these formulations. This review discusses the manufacturing processes, physicochemical properties, and other attributes of IVIG therapy that affect its clinical utility. Summary IVIG therapy is a preferred treatment for patients with certain types of primary immunodeficiency, neuroimmunologic, and autoimmune hematologic disorders, as well as for immunomodulation in bone marrow and some solid organ transplants. The IVIG products available in the United States include lyophilized, 5% liquid, and 10% ready-to-use liquid formulations. Differences among these formulations in their manufacturing processes, excipients, pH, and physicochemical properties may be reflected as differences in clinical efficacy, safety, and tolerability. For example, compared with lyophilized and 5% liquid IVIG formulations, 10% ready-to-use IVIG liquid formulations may be associated with better tolerability because of lower IgA concentrations, optimal pH, use of glycine or proline stabilizers, low sodium content, and less osmolality. Liquid formulations (both 5% and 10%) may provide greater convenience than lyophilized formulations for both patients and health care providers, because they do not require further dilution before administration and have shorter infusion times. Conclusion Before selecting an IVIG product for a hospital formulary, pharmacists should be knowledgeable about the product's concentration to ensure delivery of the proper dosage, the staff training needed for proper administration, the potential benefits and problems of brand substitution, the safety and efficacy of each formulation, the hospital's policies on off-label use of IVIG, and the impact of reimbursement.