The Serbian defending champion was sensationally knocked out in the second round of the Australian Open by Uzbekistan's Denis Istomin on Thursday, with the 117th-ranked Istomin ousting the six-time winner 7-6(10/8), 5-7, 2-6, 7-6 (7/5), 6-4 in 4hr 48min on Rod Laver Arena.
Here, Sport360 looks back at five other occasions where top-ranked players have been dumped out of the majors in the early rounds.
WIMBLEDON 2013 - FEDERER KNOCKED OUT IN ROUND TWO
Swisss star and defending champion Roger Federer was beaten 6-7 (5-7) 7-6 (7-5) 7-5 7-6 (7-5) in a four-set epic by world number 116 Sergiy Stakhovsky in the second round at SW19.
At the time, it was the 17-time Grand Slam champion's earliest exit at a major since 2003.
WIMBLEDON 2012 - NADAL OUSTED BY ROSOL POWER
Two-time SW19 winner Rafael Nadal was knocked out in a Centre Couty epic by world no100 Lukas Rosol. The Czech battled and bruised his way to a famous 6-7 (9-11) 6-4 6-4 2-6 6-4 win.
FRENCH OPEN 2009 - SODERLING DOWNS NADAL
Super Swede Robin Soderling became the first man to beat Rafael Nadal at Roland Garros, dashing the Spaniard's hopes of winning a fifth title in a row. Nadal was powered off the court at the fourth-round stage as Soderling made his way through to the final, losing to Federer.
WIMBLEDON 2003 - LLEYTON HEWITT SENT PACKING IN OPENER
The Australian defending champion became only the third man in history to get knocked out in the first round of his title defence - losing to big-serving Croatian Ivo Karlovic, 6-7 (9-11) 6-4 6-4 2-6 6-4.
WIMBLEDON 2002 - SAMPRAS'S WIMBLEDON CAREER ENDS IN DEFEAT
There was to be no fairrytale ending at Wimbledon for the seven-time SW19 champion as Swiss player Bastl, the world no145 and lucky loser qualifier, beat the American in five sets on Court 18.
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