A long-standing feud between the Montagues and the Capulets flares up in a brawl on the streets of Verona, halted only by the arrival of Prince Escalus. Romeo, only son of the Montagues, is hopelessly in love with the unattainable Rosaline. Attempting to shake him out of his melancholy, his friends Mercutio and Benvolio persuade him to go to a party at the Capulets' house. There he meets and falls instantly in love with Juliet, the Capulets' only daughter, and she with him. With the help of Juliet's Nurse, they are secretly married the next day by Friar Laurence. Juliet's cousin Tybalt quarrels with Romeo and in the fight which ensues Mercutio is killed. Romeo avenges his friend's death and kills Tybalt, for which he is banished from Verona on pain of death. After spending a single night with his bride, he escapes to Mantua. Juliet learns that her parents plan to marry her to Count Paris. Distraught, she turns to Friar Laurence, who devises a plan. He gives her a drug which will make her appear to be dead. The intention is that her parents will place her in the family tomb and when she awakes from her drugged sleep, Romeo will be waiting to escape with her to Mantua. When Romeo returns to Verona, he believes her really to be dead and kills himself. Waking to find Romeo dead beside her, Juliet kills herself. The two families, united in grief, vow to end their feud.
De Vere became entangled in a love affair that led to an interfamily war, like the war between the Montagues and Capulets.
Friar Laurence is based on de Vere's Protestant tutors Sir Thomas Smith and Laurence Nowell. Sir Thomas Smith, like Friar Laurence, was adept at making tinctures and tonics. Not coincidentally, Friar Laurence is the only papist authority figure in Shakespeare that is treated with respect and authority. In other words, respect of former teachers outweighs religious concerns.
In December 1574, Anne Cecil fell sick and there were fears she might die. Sir Thomas Smith sent Anne a potion. Anne recovered. Smith practiced Paraclesian medicine - a new and empirical approach to healing based on distillations of chemicals and essences. In 16th century England, the Paraclesians were considered quacks.
De Vere's supporters were at war with Knyvet and his supporters in 1582. De Vere and Thomas Knyvet had a duel in which both were injured, and one of de Vere's servants was killed. Some men claiming to be employees of de Vere began to attack members of Knyvet side, starting with Rocco Bonetti, who was known for introducing a form of Italian swordmanship to England. Bonetti sought protection from de Vere's men. In 1584, two supposedly retainers of de Vere - Gastrell and Horsley - attacked Knyvet and four associates in Blackfriars. Four days later, there was another skirmish between Gastrell and another man Harvey. Romeo and Juliet begins after three brawls between the Montagues and the Capulets. In the words of the Prince:
Three civil brawls bred of an airy word
By thee, old Capulet and Montague,
Have thrice disturb'd the quiet of our streets
And made Verona's ancient citizens
Cast by their grave-beseeming ornaments
To wield old partisans, in hands as old,
Canker'd with peace, to part y our canker'd hate.
If ever you disturb our streets again
Your lives shall pay the forfeit of the peace.
Romeo and Juliet then reports a subsequent melee where as Montague falls. A slain servant of de Vere's is buried eight months after the Blackfriars fight. Subsequently, a Capulet is slain. (Burghley reports the death of one of Knyvet's servants a month after de Vere's man is slain. In Romeo and Juliet, there is another challenge to a duel. De Vere was challenged to another duel by Knyvet, and does not answer and the interfamily war ends.
As a result of the brawls, Romeo is banished from Mantua. By the end of 1582, de Vere is expelled from court, and low on money, much like Romeo.
Juliet was a young bride, as was Anne Cecil when she married de Vere at 15 years.
The play toys with the idea of "atomies" as nature's unit of irreducible smallness. De Vere's only known secretary in his later years was Nicholas Hill. Hill was ridiculed around London as the leading advocate of Democritus's atomic philosophy.
In 1575, De Vere visited Venice, which was suffering an epidemic of bubonic plague. Those in contact with victims were quarantined for 40 days. The textile industry closed down. The city lost a quarter of his inhabitants. Church spires across the Veneto glowed with "lanterns of the dead" - an Italian funeral tradition that appears in Romeo and Juliet.