Presently cancer is a grave health issue with predominance beyond restrictions. It can affect any organ of the body. Most of the available chemotherapeutic drugs are highly toxic, not much selective and eventually lead to the development of resistance. Therefore, a target specific palliative approach for the treatment of cancer is required. Remarkable advancements in science have illuminated various molecular pathways responsible for cancer. This has resulted in abundant opportunities to develop targeted anticancer agents. Quinazoline nucleus is a privileged scaffold with significant diversified pharmacological activities. Numerous established anticancer quinazoline derivatives constitute a new class of chemotherapeutic agents which are found to act by inhibiting various protein kinases as well as other molecular targets. A recent update on various quinazoline derivatives acting on different types of molecular targets for the treatment of cancer has been compiled in this review. Brief SAR studies of quinazoline derivatives acting through different mechanisms of action have been highlighted. The comprehensive medicinal chemistry aspects of these agents in this review provide a panoramic view to the biologists as well as medicinal chemists working in this area and would assist them in their efforts to design and synthesize novel quinazoline based anticancer compounds.