The blood-brain barrier (BBB) protects the brain from pathogenic microorganisms. Neurologic complications from viral infections, including herpes simplex virus, varicella zoster virus, HIV, Japanese encephalitis virus, and SARS-CoV-2, are linked to BBB dysfunction and loss of barrier integrity. Increased BBB permeability associated with viral infections can occur through several mechanisms, such as direct neurotropism, Trojan horse mechanisms, or systemic infection and inflammation. Viruses cause direct and indirect immune-mediated damage. Understanding these neuroimmune mechanisms is critical to establish therapeutic strategies to protect BBB function. This review describes the effect of viral infection on the BBB, clinical methods to assess BBB integrity, and clinical management approaches to address viral-induced BBB damage.