Liver fibrosis is a serious health issue for many liver patients and is currently diagnosed using liver biopsy. The erroneous nature of this technique urges the search for better, noninvasive alternatives. In this regard, proteomics has been described as a useful biomarker discovery tool and has become increasingly applied in the study of liver fibrosis. Experimental and clinical studies have already provided deeper insights in the molecular pathways of liver fibrosis and even confirmed previous findings. Recent advances in proteomic strategies and tools enable multiple fractionation, multiple protein identifications and parallel analyses of multiple samples. Despite its increasing popularity, proteomics still faces certain pitfalls concerning preanalytical variability, protein coverage and statistic reliability. Proteomics is still evolving, but will undoubtedly contribute to a better understanding of the basis of the pathology and certainly offer opportunities in liver fibrosis diagnostics and therapeutics.