His ruthless maneuvering during a decade and a half in the presidency, since 1991, has also allowed him to keep potential rivals off-balance.
James Nixey, who heads the Russia and Eurasia program at the London-based think tank Chatham House, says Karimov's tight grip on power and frequent government reshuffles have prevented other senior officials from accruing public sympathy.
'Tried Old Method'
More recently, Nixey says, Karimov has succeeded in weakening the clans, and does not appear vulnerable to a palace coup.
"I very much doubt that Karimov is taking his eye off the ball to such an extent that he would let [a palace coup] happen," Nixey says. "And the changes in the upper echelons of Uzbek politics which we have seen relatively recently indicate that the tried old method of switching one's ministers around -- ensuring that nobody gets too settled in one place, nobody becomes too powerful -- does ensure that the Karimov regime may well last for as long as he lives."
Observers also tend to rule out any popular uprising like the one that deposed a president in neighboring Kyrgyzstan in 2004.
Nixey says the Uzbek public learned a lesson when a minor uprising in the eastern city of Andijon led to a deadly crackdown in May 2005.
Craig Murray, a former British ambassador to Tashkent and an outspoken critic of Karimov's regime, says ordinary Uzbeks and government officials alike fear bloodshed similar to that seen in Andijon.
"If people take the decision to remove Karimov by violence -- and there are plenty of indications that there are quite a number of people in the [state security service], in the military, [and] in the Ministry of Interior who might well support such a move -- but any move is going to have to be prepared very, very carefully. Because what nobody wants are more 'Andijons,'" Murray says.
One of Karimov's early challenges came from a powerful politician and former mentor from his own Samarkand clan, Ismoil Jurabekov. But Jurabekov's political career came to an abrupt halt when he was dismissed as a presidential adviser in 2004 under a cloud of criminal allegations.
The Samarkand clan suffered another political blow when Interior Minister Zokir Almatov resigned in late 2005, citing poor health. Almatov had been the longest-serving minister in the government, and police backing made him a powerful figure.
Karimov appointed a deputy director of the Uzbek National Security Service (SNB) to replace Almatov. The move was a bold political stroke, since the SNB is a rival institution to the Interior Ministry -- and also a power base of the Tashkent clan.
Karimov further weakened the Tashkent clan by forcing Defense Minister Qodir Gulomov to resign in November 2005. In May, authorities tried him behind closed doors and sentenced to a suspended prison term -- reportedly on charges of fraud, corruption, and abuse of office.
Gulomov's resignation came soon after the dismissal of his close relative and a onetime leader of the Tashkent clan, Timur Alimov, from a presidential advisory post.
Former ambassador Murray tells RFE/RL that a dwindling number of people exercise any real power in Uzbekistan.
"There are a lot of people who used to be in the oligarchy," Murray says. "There were a couple of hundred very wealthy families who really benefited from the system. That circle has got smaller and smaller and smaller as Karimov narrows it down toward his immediate family."
Murray says economic capital has been concentrated mainly in the hands of Karimov's eldest daughter.
Gulnora Karimova is believed to control major businesses in Uzbekistan -- including in oil, gas, and telecommunications.
But Murray, who authored a book titled "Murder In Samarkand" that chronicles Karimov's reign and his own tenure as ambassador to Uzbekistan, argues that the situation has led to the emergence of discontented politicians who are now seeking to remove Karimov from office. Unlike some others, Murray does not dismiss the risks of a violent ouster.
"There are a lot of people I call 'the new losers,'" Murray says. "And if you look at the people who were very close to Karimov a few years ago, many of them have now been thrown out; and, in particular, their economic interests and assets have often been diverted to Gulnora. And there now are a lot of people who used to be very important who now have an interest in seeing Karimov go. So, one definite possibility what we might come to is the palace coup -- where he simply gets a bullet in the back of the head."
Bahodir Musaev is an independent sociologist based in the Uzbek capital, Tashkent. He agrees that Karimov's system of absolute power poses a danger from within, albeit in arguably less stark terms.
"He is in fact absolutely lonely -- nobody likes this person," Musaev says. "And I think if his health worsens, his family will be torn to pieces."