Sclerotinia sclerotiorum is a typical necrotrophic plant pathogenic fungus that distributes worldwide and causes severe diseases on a broad-range of plant species. Studies on S. sclerotiorum have been mainly focused on biology and pathology. The development of high-throughput technologies enabled multi-omics approaches for systems biology. This review summarizes current researches on S. sclerotiorum and proposes systemic strategies for understanding its biology and pathology, to provide novel insights and references for further investigation on molecular biology and pathogenesis of the pathogenic fungi and the pathosystems.