The 16-game South American FIFA World Cup qualifying campaign can be a marathon but the continent's leading nations can take big strides towards sealing their places in the 2014 finals this month.
There are four automatic qualifying slots available for the tournament in Brazil, as well as a play-off against an Asian nation as a consolation for fifth place.
With its old rival not having to qualify, all the pressure is on Argentina, which hosts Paraguay in Cordoba in third place in the section.
Failure to make it to neighbouring Brazil is unthinkable for Argentina but Lionel Messi is not taking anything for granted, especially after forming part of the sides that slipped up against supposed outsiders Bolivia and Venezuela earlier in the campaign.
"The qualifiers are tough regardless of what kind of form your opponents are in," he warned ahead of the Paraguay clash.
"We knew that changes needed to be made after the game against Bolivia (a 1-1 draw in November last year) because of the result and because of the way we played.
"But we did that and we have since won some difficult games against good teams."
Paraguay's run to the Copa America final in Argentina last year is now but a distant memory after its miserable start to World Cup qualifying.
A run of just one win and three defeats in its opening five matches led to coach Francisco 'Chiqui' Arce being sacked.
His replacement is Gerardo Pelusso, and the experienced Uruguayan is determined to turn around the fortunes of his new charges.
With group leader Chile not in action until its home clash with Colombia next midweek, Uruguay can go clear at the top of the table with a win against the Colombians in Barranquilla.
The reigning continental champion, which warmed up for the game with a goalless friendly in France last month after a disappointing showing at the Olympics, is the only side in South American qualifying still defending an unbeaten record.
"These games will be fundamental. If we can take something in Colombia and then win at home (against Ecuador) we will have taken a huge step towards making it to Brazil," said defender Diego Godin.
Ecuador currently holds the fourth and final automatic qualification berth, largely thanks to its impressive home form at altitude in Quito.
However, its weekend opponent Bolivia is no strangers to playing in rarefied air and will be out to impress under new Spanish coach Xabier Azkargorta, who led the greens to the 1994 finals in the USA.
Venezuela, which has already held Uruguay and beaten Argentina, continue its quest to qualify for a first major tournament finals when it goes to bottom-of-the-table Peru.
WC Qualifying CONMEBOL
Argentina fought back from a goal down to claim a potentially valuable 1-1 draw from its 2014 FIFA World Cup qualifier in Bolivia, while Luis Suarez hit the headlines for the wrong reasons as Chile beat Uruguay.