Lucius Aelius Sejanus is portrayed by the main ancient sources as a sinister figure, likely because of his ambition and ancestry.

Of equestrian and aristocratic origin, he began his rise as Praetorian Prefect shortly after Tiberius's accession. Between AD 20 and 23, he centralised the Praetorian Cohorts in Rome, which had previously been scattered across Italy. He built the Castra Praetoria, a vast barracks outside the city to house them all. This reform ensured the emperor always had his guard nearby, but it also transformed the Praetorians into a powerful political instrument used by both the princeps and, above all, the prefect. Sejanus also introduced the scorpion, Tiberius's zodiac sign, as their emblem.

Over time, Sejanus became one of Tiberius's closest advisers and, according to Tacitus, the lover of Drusus the Younger's wife, Livilla. Tiberius's heir died in AD 23 after an illness; Tacitus claims he was poisoned by Sejanus and Livilla. With the deaths of the main heir and Tiberius's nephew Gemellus, whom Sejanus may have hoped to rule as regent, only Nero and Drusus, the sons of Germanicus, remained. Ancient sources state that Sejanus fuelled Tiberius's paranoia, encouraging him to persecute Germanicus's family. The only author favourable to Sejanus is Velleius Paterculus, who probably suffered after the prefect's fall. When Tiberius retired to Capri, Sejanus effectively controlled Rome and eliminated his rivals: Nero was forced to commit suicide, Drusus died imprisoned beneath the Palatine, and their mother, Agrippina the Elder, perished in exile on Ventotene.

Sejanus later asked to marry Livilla, but Tiberius rejected the proposal because of their different social ranks. This marked the beginning of his downfall. Through Antonia the Younger, mother of Germanicus and Livilla, Tiberius was likely informed of Sejanus's alleged ambitions. Supported by the future prefect Macro and perhaps by his nephews Gaius (Caligula) and Claudius, the emperor laid a trap: after Macro convinced Sejanus he would receive tribunician power, Tiberius denounced him before the Senate for treason and conspiracy. Sejanus was strangled in the Mamertine Prison, and his family was executed. Livilla, confined by her mother, eventually died of starvation.