Various classes of cytotoxic compounds which alkylate cellular thiols are described namely alpha,beta-unsaturated ketones, alpha-methylene-gamma-lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be influenced by modulation of the concentration of thiols including the observation that potencies can be increased by thiol activation. The ability of certain thiol reagents to reverse multidrug resistance as well as some miscellaneous actions of thiol alkylators are described.