The winners of the nine European groups qualify directly for Brazil next year and the eight best runners-up go into two-leg playoffs for four more places.
The campaign has already produced several surprises, no more so than in Group H where tiny Montenegro, who played their first full international only six years ago, top the table with four wins and two draws in six matches.
They will take a five-point lead over second-placed England if they can beat Ukraine at home, leaving Roy Hodgson's team with the unappetising prospect of a two-leg playoff to reach Brazil.
Third-placed Poland could also close the gap on England to one point if they win in Moldova, putting further pressure on Hodgson's team.
Group G leaders Bosnia, who have 13 points from five games, should be too strong as they visit lowly Latvia with Greece, who are three points behind them, travelling to Lithuania
Bosnia, who joined FIFA in 1996 and have yet to qualify for a major tournament, have blasted 18 goals so far, 12 of them coming from their strikeforce of Edin Dzeko and Vedad Ibisevic.
Either Iceland or Albania (nine points each) could go top of Group E, at least until current leaders and favourites Switzerland (11) points host Cyprus the following day.
Iceland are at home to Slovenia while Albania host Norway, who they have already beaten 1-0 in Oslo in the first of several upsets in the group.
Switzerland coach Ottmar Hitzfeld will on the touchline for Saturday's game in Geneva as he serves the second of a two-match ban for insulting the referee in an earlier game.
Television cameras showed the usually unflappable Hitzfeld sticking his middle finger - known in German as the "Stinkefinger" - at the official at the end of the 1-1 draw against Norway in November.
Two of Europe's most volatile strikers come face to face in Vienna as Austria's Marko Arnautovic lines up against Sweden's Zlatan Ibrahimovic in Group C.
Arnautovic has been included in Austria's squad despite missing the last three matches of the season for Werder Bremen after he was caught speeding on a German motorway.
Austria, Sweden and Ireland are level on eight points in Group C, eight behind the rampant Germans. The Irish host pointless Faroe Islands the same evening.
"We can say this is an acid test for us," Austria defender Alexsandar Dragovic told reporters. "We have played very well in the last few games and now it's time to take the next step and beat Sweden."
Portugal, who are one point behind Russia and have played two games more, need to win their match to have any realistic chance of finishing top of the group. Israel, level on 11 points with Portugal, are not playing.
Belgium and Croatia, who have turned Group A into a two-horse race, both have home matches, the Belgians facing Serbia and Croatia hosting Scotland. Both teams have 16 points, nine clear of Serbia, and are unbeaten.
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