Over the past few years, we have achieved increasing success in the treatment of a number of autoimmune-mediated disorders affecting nerves and muscles. This success is partly attributable to the use of high-dose polyclonal intravenous immunoglobulin (IVIg), which has dramatically changed our treatment options. On the basis of results from controlled, but non-FDA-approved, clinical trials, IVIg is now the treatment of choice for Guillain–Barré syndrome, chronic idiopathic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy; IVIg offers rescue therapy for patients with rapidly worsening myasthenia gravis, and is a second-line therapy for dermatomyositis, stiff-person syndrome, and pregnancy-associated or postpartum multiple sclerosis attacks. The ability of IVIg to treat such immunologically diverse disorders effectively, coupled with its excellent safety profile, has led clinicians to use the drug more liberally, even in diseases for which the data are weak and not evidence-based and in patients with coexisting conditions. Use of IVIg for such indications can increase the risk of complications while raising the cost of the drug. Practical issues regarding dosing and frequency of infusions generate dilemmas in clinical practice. In this article, we review the current indications for IVIg treatment, address practical issues related to the use and costs of the drug, and summarize its mechanisms of action.