Severe Guillain-Barré syndrome can produce rapid respiratory failure and profound disability despite standard treatment with IVIG or plasma exchange. A phase 3 randomized, double-blind, placebo-controlled trial evaluated whether adding eculizumab, a complement C5 inhibitor, to IVIG improved outcomes in severely affected adults. The trial did not establish a clear overall efficacy advantage sufficient to change routine standard-of-care management. This result is important because complement activation has a strong biological rationale in GBS, but mechanistic plausibility does not automatically translate into clinical benefit. For HCPs, the established priorities remain early recognition, respiratory monitoring, autonomic surveillance and timely standard immunotherapy. Patients who deteriorate rapidly require escalation of supportive care even when immunotherapy has already begun. The eculizumab study also illustrates the challenge of conducting trials in heterogeneous acute immune neuropathies, where disease severity, timing of treatment and biological subtype may influence response. For neurologists, emerging targeted therapies should therefore be considered investigational until robust evidence demonstrates meaningful improvements in recovery or survival.