Skin cancer is a life threatening disease and their prevalence and risk has been increasing over the past three decades causing significant loss to human health worldwide. Mostly skin cancer has developed resistance against chemotherapy and radiotherapy. Therefore, development of novel, cost effective and efficient treatment methods are needed. Phytochemicals extracted from medicinal plants and dietary sources are often biologically active and has attracted the attention of researchers and pharmaceutical industries around the world. Many in vitro and in vivo studies of these bioactive compounds have shown potential antioxidant, anti-proliferative, anti-inflammatory and anti-angiogenic effects in the fight against skin cancer. These phytochemicals also regulate several other molecular processes such as angiogenesis, metastasis and cell cycle to combat skin cancer. The present review provides perspectives on the key phytochemicals, their therapeutic potentials, bioavailability and molecular mechanism of action in the cancer therapeutics. Current challenges and future directions for research are also critically discussed.