Alkylating　agents　are　genotoxic　chemicals　that　can　induce　and　treat　various　types　of　cancer.　This　occurs　through　covalent　bonding　with　cellular　macromolecules,　in　particular　DNA,　leading　to　the　loss　of　functional　integrity　under　the　persistence　of　modifications　upon　replication.　O6-alkylguanine　(O6-AlkylG)　adducts　are　proposed　to　be　the　most　potent　DNA　lesions　induced　by　alkylating　agents.　If　not　repaired　correctly,　these　adducts　can　result,　at　the　molecular　level,　in　DNA　point　mutations,　chromosome　aberrations,　recombination,　crosslinking,　and　singleand　double-strand　breaks　(SSB/DSBs).　At　the　cellular　level,　these　lesions　can　result　in　malignant　transformation,　senescence,　or　cell　death.　O6-methylguanine-DNA　methyltransferase　(MGMT)　is　a　DNA　repair　protein　capable　of　removing　the　alkyl　groups　from　O6-AlkylG　adducts　in　a　damage　reversal　process　that　can　prevent　the　adverse　biological　effects　of　DNA　damage　caused　by　guanine　O6-alkylation.　MGMT　can　thereby　defend　normal　cells　against　tumor　initiation,　however　it　can　also　protect　tumor　cells　against　the　beneficial　effects　of　chemotherapy.　Hence,　MGMT　can　play　an　important　role　in　both　the　prevention　and　treatment　of　cancer;　thus,　it　can　be　considered　as　a　double-edged　sword.　From　a　clinical　perspective,　MGMT　is　a　therapeutic　target,　and　it　is　important　to　explore　the　rational　development　of　its　clinical　exploitation.