During the talks in the ancient Silk Road city of Bukhara, the two leaders are set to sign an agreement pledging "eternal friendship" between their countries.
Yet their personal relationship has been anything but friendly, according to Central Asia specialist Gregory Gleason of the University of New Mexico in the western U.S. city of Albuquerque.
"These two leaders, who knew each other relatively well during the Soviet period because they were both Communist Party first secretaries, have over the years drifted further and further apart and have become really, as far as we can tell from what information is available in the public record, have become very personally antagonistic toward one another," Gleason said.
The choice of Bukhara underscores the uneasy relations between the presidents. Neither reportedly wants to be seen making the trip to the other's capital and so have settled on Bukhara, located about halfway between the Turkmen capital Ashgabat and Tashkent in Uzbekistan.
There are numerous stories about the animosity between the two leaders. But it wasn't until two years ago that relations between their countries hit an all-time low.
Days after an assassination attempt on Niyazov in late November 2002, Turkmen security agents raided Uzbekistan's embassy in Ashgabat.
Uzbekistan's Foreign Ministry protested. But the Turkmen Prosecutor General's Office accused the Uzbek embassy of hiding Boris Shikhmuradov -- a former Turkmen foreign minister who had become an opposition leader in exile and was the alleged chief plotter behind the attempt to kill Niyazov.
Shikhmuradov was later caught, in Turkmenistan, and confessed that he had crossed into the country from Uzbekistan with help from people there. Uzbekistan's ambassador was declared a persona-non-grata and ordered out of Turkmenistan.
Shortly thereafter, Niyazov spoke publicly about Turkmen relations with Uzbekistan.
"We respect the Uzbek people very much. The Uzbek people cannot be blamed, but their leadership helped the terrorist [Boris] Shikhmuradov cross into our country. But we are living as neighbors with the Uzbek people and even if their leaders do the wrong thing, we will live with the Uzbek people. We will keep our relationship with them as brothers," Niyazov said.
For his part, Karimov has never been very diplomatic in his comments about Central Asian leaders including Niyazov, who is referred to in Turkmenistan as "Turkmenbashi" -- literally, the head of the Turkmen, but often translated as "father of the Turkmen."
Recently, Karimov chided a member of parliament for using the term "Ata," the more common word for father among the region's Turkic peoples. However, "Ata" is also used to denote affection toward a leader or elder -- a designation that Karimov took offense to.
"You addressed me as 'Ata.' This is pleasant to hear as it is an honorable way of addressing someone, it shows respect. But from the point of view of governance this word Ata is understood from history, from archives. If a president is called Ata, in the capacity of father, then you can't call this government a democracy. That is a khanate. Some of our neighbors have to do this because it is required. All questions are decided by the president. Why? Don't they have a system of government there?" Karimov said.
Such remarks reflect tensions that have been built up since the first years of independence -- and expressed in odd ways.
As early as 1992, Turkmen authorities began erecting statues and portraits of Niyazov as well as naming streets and buildings after the president. All of this helped create the "cult of personality" that Niazov enjoys to this day.
But months later, in reaction to these developments, Karimov told the Uzbek parliament that it would be illegal to have statues of a living person placed anywhere in Uzbekistan.
In 1996, the Economic Cooperation Organization held its summit in Ashgabat. As Karimov headed there aboard a new presidential plane, Turkmen air traffic controllers radioed to say there was a problem and Karimov's plane would have to be re-routed to land at a secondary airport in Turkmenistan.
Karimov's plane was eventually allowed to land in Ashgabat. But none of the other leaders attending that summit had any trouble reaching the Turkmen capital.
Currently, the border issue is a prime source of tension between the two nations
Smuggling of cheap Turkmen gasoline to Uzbekistan is a thriving business. There have been several recent occasions where Turkmen border guards have beaten and even shot Uzbek citizens crossing the border illegally, usually carrying gasoline.
Last September, the Turkmen president suggested that the situation along this border was even more problematic. He told a meeting of Interior Ministry officials that more needed to be done to stop illegal weapons trafficking.
It was the first public acknowledgment of the issue, which seems certain to be discussed when the leaders meet tomorrow.
Karimov is also likely to address Turkmenistan's latest water diversion plans.
Turkmenistan is building an artificial reservoir in the desert. The government says no extra water will be required from the Amu-Darya river that both countries share, but there are doubts that this is feasible.
Overuse of the Amu-Darya's water has already contributed to the desiccation of the Aral Sea and has had dire consequences for the people living in northwestern Uzbekistan.
(Rozinar Khoudaiberdiev and Yovshan Annagurbanov of the Turkmen Service contributed to this report)