The quote, “Then I defy you, stars,” was made after Romeo learned that Juliet was dead. By stars, he meant fate. There are multiple references to fate throughout the play. Earlier, Romeo and Juliet are referred to as “star-crossed lovers” and it is foreshadowed that they will take their own lives. After Romeo kills Tybalt in a fight he never wanted to have, he cries out, “O, I am fortune’s fool!” The quote about defying the stars is the third such obvious reference. In addition, there are numerous examples of fate standing between the lovers in Act 5 scene i-ii. There was no real reason that the friars plan should not have worked, and yet a series of missed opportunities causes the end that we know. With this quote, Romeo is declaring himself in opposition to destiny, although his resulting actions actually bring it about. Romeo commits suicide, prompting Juliet to do the same, which fulfills the tragic destiny of the star-crossed lovers.
"Is it e'en so? Then I defy you, stars!
In Act V scene I Romeo has just found out that Juliet is dead. He is beside himself with grief and he curses "I defy you, stars," which means he denies fate. He denies fate's hold on him and he then plans to kill himself. He goes to buy poison and goes to Juliet's tomb. Later in Act V scene III Romeo again refers to the stars when he talks about the "inauspicious stars," referring again to fate, or as in this case, unlucky stars. This is of course the beginning of the end for the "star crossed lovers."