In recent times, a number of studies have provided evidence that biotoxins present great potential as antitumoragents, such as snake venom, bee venom, some bacteria toxins and plant toxins, and thus could be used aschemotherapeutic agents against tumors. The biodiversity of venoms and toxins make them a unique source fromwhich novel anticancer agent may be developed. Biotoxins, also known as natural toxins, include toxic substancesproduced by plants, animals and microorganisms. Here, we systematically list representative biological toxinsthat have antitumor properties, involving animal toxins, plant toxins, mycotoxins as well as bacterial toxins.In this review, we summarize the current knowledge involving biotoxins and the active compounds that haveanti-cancer activity to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumorcells in vivo or in vitro. We also show insights into the molecular and functional evolution of biotoxins.