Organic sulfur compounds (OSCs) derived from plants, fungi or bacteria can serve as chemopreventive and/or chemotherapeutic agents and have been attracting medical and research interest as a promising source for novel anti-cancer agents. Garlic, which has long been used as a medicinal plant in different cultures due to its multiple beneficial effects, contains a consistent number of OSCs, the majority of which are currently under investigation for their biological activities. Experimental animal and laboratory studies have shown strong evidence that garlic OSCs may affect cancer cells by promoting early mitotic arrest followed by apoptotic cell death without affecting healthy cells. The ability of OSCs to hinder cancer cell proliferation and viability tightly correlates with the length of the sulfur chain. Current data support a mechanism of mitotic arrest of cancer cells due to the alteration of the microtubule network, possibly as a consequence of the high reactivity of sulfur atoms against the thiol groups of different cellular macromolecules controlling crucial regulatory functions. Taken together, these findings indicate a promising potential for the use of garlic-derived sulfur compounds in chemoprevention and chemotherapy.