Treatment of cancer with chemotherapy has two main problems: toxicity to normal cells and failure to kill cancer cells. Cancer cells are characterized by uncontrolled cells proliferation and unlimited life span. Development of anti-cancer drug should involve the search for compounds capable of halting cell proliferation and/or leading to cell death. Combination of both types of drugs will make efficient chemotherapy. The compounds selected in this study are unique in their mode of action: they activate the protein procaspase-3, a critical enzyme in cell death process known as: apoptosis or programmed cell death. Although programmed cell death occurs naturally, too much or too little apoptosis cause diseases. Not enough apoptosis cause cancer. Apoptosis involves a cascade of enzymes (caspases) that are made as latent zymogens (pro-enzymes); procaspases activated following apoptotic death stimuli, lead to cleavage of cellular proteins, cleavage of DNA and cell death. The enzyme caspase-3 acts in a point of no return in this cascade. As such, compounds that will activate caspase-3 will be considered as potential anti-cancer drugs. In practice, for a compound to be considered as a potential lead drug, it should be a small molecule, stable, selective, and able to penetrate cellular membranes effectively. Following screening of plant extracts against several cancer models and through development of an assay that can detect compounds which activate caspase-3, several extracts capable of killing cancer cells by activating caspase-3 were identified.