The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin Ddimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.