HIV-1　membrane　fusion　as　a　part　of　the　process　of　viral　entry　in　the　target　cells　is　facilitated　by　gp41　and　gp120,　which　are　encoded　by　Env　gene　of　HIV-1.　Based　on　the　structure　and　the　mechanism　researches,　new　treatment　options　targeting　HIV-1　entry　process　have　been　proposed.　Enfuvirtide,　which　mimics　amino　acid　sequences　of　viral　envelope　glycoprotein　gp41,　is　the　first　HIV-1　fusion　inhibitor　approved　by　FDA.　Although　it　fulfills　vital　functions　by　binding　to　gp41　and　abolishing　the　membrane　fusion　reaction　when　used　in　combination,　it　could　induce　drug　resistant　virus　variants.　Currently,　a　number　of　design　and　modification　schemes　have　been　presented,　a　large　number　of　prospective　fusion　peptides　have　emerged.　For　these　fusion　inhibitors,　multiple　mutations　in　gp41　have　been　associated　with　the　loss　of　susceptibility　to　agents.　This　review　reported　the　current　developments　and　innovative　designs　of　HIV-1　membrane　fusion　inhibitors.