Cancer is the leading cause of death worldwide and a serious metabolic illness. Finding novel compounds that are optimally harmful to cancer cells but not to healthy ones has become crucially important. Plant-based medications continue to be an important source for the treatment of severe ailments, especially in developing countries. Traditional medicine has a long history and is still widely used in Yemen to treat a wide range of illnesses. Flora of Yemen is rich in endemic and semi-endemic plants, constituting about 16% of Yemeni plants which recorded 2838 plant species belonging to 179 families. Therefore, the present review aims to summarize the cytotoxic plants available in Yemen. The review covers 229 species, belongs to 163 genera and 72 families collected from several localities in Yemen. Most of studies showed high and intermediate activity against 44 different cancer cell lines such as liver, and breast using different assays and different extraction solvents as well as over 7 isolated bioactive cytotoxic compounds. Current study concluded that Yemeni medicinal plants are considered as an underutilized source of medicines for treating cancer. Further great efforts are required to evaluate the effectiveness of different Yemeni plants on several cancer cell lines, to isolate and identify the chemical compounds responsible for such activity.