Sepsis-associated acute lung injury (SALI) is a common complication of sepsis, consisting of a dysfunctional host response to infection-mediated heterogenous complexes. SALI is reported in up to 50 % of patients with sepsis and causes poor outcomes. Despite high incidence, there is a lack of understanding in its pathogenesis and optimal treatment. A better understanding of the molecular mechanisms underlying SALI may help produce better therapeutics. The effects of altered cell-death mechanisms, such as non-apoptotic regulated cell death (RCD) (i.e., ferroptosis), on the development of SALI are beginning to be discovered, while targeting ferroptosis as a meaningful target in SALI is increasingly being recognized. Here, we outline how a susceptible lung alveoli may develop SALI. Then we discuss the general mechanisms underlying ferroptosis, and how it contributes to SALI. We then outline the chemical structures of the emerging agents or compounds that can protect against SALI by inhibiting ferroptosis, summarizing their potential pharmacological effects. Finally, we highlight key limitations and possible strategies to overcome them. This review suggests that a detailed mechanistic and biological understanding of ferroptosis can foster the development of pharmacological antagonists in the treatment of SALI.