Abstract Background Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. Whilst the literature addressing PHLF appears ubiquitous, there is no specific structure that summarizes the evidence that can guide surgeons regarding the timeline of the preventive measures against PHLF. The objective of this review is to summarize the published measures and their sources of evidence, in a timeline centered way around the index (i.e., definitive) hepatectomy, thus, summarizing the practice in prediction, prevention, and treatment. Methods This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black’s checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. Results This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. Conclusions Remnant liver volume manipulation is the most consistent preventive measure against PHLF.