Sepsis is a common phenomenon surrounded by uncertainty and misunderstanding. The urgency for treatment is complicated by the vagueness of signs and symptoms and lack of a conclusive diagnostic test. This article unpicks the signs and symptoms of sepsis with guidance for emergency department nurses who are responsible for assessing patients with potential sepsis. The article also relates monitoring, investigation and treatment expectations to the underlying pathophysiology and refers to the individual and global implications of the condition. ©2019 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.