Atthebeginningof2259,CaptainJohnSheridanreplacesSinclairasthemilitarygovernorofthestation.HeandthecommandstafflearnthatthedeathofPresidentSantiagowasactuallyanassassinationmastermindedbyVicePresidentClark(whoassumedthePresidencyuponSantiago'sdeath).AconflictdevelopsbetweentheBabylon5commandstaffandthePsiCorps,anincreasinglyautocraticorganizationwhichoverseesandcontrolsthelivesofhumantelepaths.CommanderIvanova,thesecond-in-commandofthestation,issecretlyalatenttelepathwhohasillicitlyavoidedregisteringwiththePsiCorps. TheShadows,anancientandextremelypowerfulracewhohaverecentlyemergedfromhibernation,arerevealedtobethecauseofavarietyofmysteriousanddisturbingevents,includingtheattackontheNarnoutpostattheendof2258.CentauriAmbassadorLondoMollariunknowinglyenliststheiraidthroughhisassociationwiththemysteriousMr.MordenintheongoingconflictwiththeNarn.TheelderlyandailingCentauriemperor,longanadvocateofreconciliationwiththeNarn,diessuddenlywhilevisitingBabylon5.Anumberofconspirators,includingLondoMollariandRefa,takecontroloftheCentaurigovernmentbyassassinatingtheiropponentsandplacingthelateemperor'sunstablenephewonthethrone.TheirfirstactistostartopenaggressionagainsttheNarn.Afterafull-scalewarbreaksout,theCentaurieventuallyconquerNarninabrutalattackinvolvingmassdrivers,outlawedweaponsofmassdestruction.Towardstheendoftheyear,theClarkadministrationbeginstoshowincreasinglytotalitariancharacteristics,clampingdownondissentandrestrictingfreedomofspeech.TheVorlonsarerevealedtobethebasisoflegendsaboutangelsonvariousworlds,includingEarth,andaretheancientenemiesoftheShadows.TheyenlisttheaidofSheridanandtheBabylon5commandstaffinthestruggleagainsttheShadows.
