Sepsis is conceptually defined as life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Although there has been significant advancement in recent decades in defining and understanding sepsis pathology, clinical management of sepsis is challenging due to difficulties in diagnosis, a lack of reliable prognostic biomarkers, and treatment options that are largely limited to antibiotic therapy and fundamental supportive measures. The lack of reliable diagnostic and prognostic tests makes it difficult to triage patients who are in need of more urgent care. Furthermore, while the acute inpatient treatment of sepsis warrants ongoing attention and investigation, efforts must also be directed toward longer term survival and outcomes. Sepsis survivors experience incomplete recovery, with long-term health impairments that may require both cognitive and physical treatment and rehabilitation. This review summarizes recent advances in sepsis prognosis research and discusses progress made in elucidating the underlying causes of prolonged health deficits experienced by patients surviving the early phases of sepsis.