Williams takes on home favourite Heather Watson on centre court, with the world number one looking to continue her bid for a calendar Grand Slam.
The American has looked in good form thus far at the All England Club, dropping just ten games in total in the opening two rounds, and Watson – who is the British number one – is certainly going to have her work cut out for her.
Before Williams can step out on Centre Court, Djokovic will be up against Australian Bernard Tomic. The pair have met three times previously, with Djokovic triumphing on each occasion.
Elsewhere in the men's draw, seventh seed Raonic faces a stiff test against bad boy Kyrgios. The Australian's behaviour has been a hot topic this week, and he'll be out to make sure that his play does all the talking on Friday.
Former champion Maria Sharapova is in action on Court One, with the Russian up against Irina-Camelia Begu of Colombia.
Thursday key matches:
Grigor Dimitrov  v Richard Gasquet 
Novak Djokovic  v Bernard Tomic 
Nick Kyrgios  v Milos Raonic 
Marin Cilic  v John Isner 
Stan Wawrinka  v Fernando Verdasco
Serena Williams  v Heather Watson
Maria Sharapova  v Irina-Camelia Begu 
Sloane Stephens v Lucie Safarova 
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