Rem adopted Vash and Knives when they were little and raised them as her own. Rem is Vash’s inspiration, she’s the reason alone why he refuses to kill and finds it painful to do so.

Rem did her best to teach the little brothers all she knew about love and peace but only Vash took It to heart. About 129 years before Trigun (when Vash and Knives were little) Vash watches Rem and Knives die in an escape pod when the ship they were escaping from explodes.