Manchester United and Liverpool have had many fierce meetings over the years, but this is the first time that they face one another in a European knockout match.
Liverpool travel to Old Trafford on Thursday with a 2-0 advantage following their win at Anfield in the first leg a week ago.
The winner of Thursday's clash will progress into the quarter-finals of the Europa League.
Manchester United
Life looked a bit rosier for Louis van Gaal and his team last month when they claimed four victories in all competitions on the bounce.
Many believed that fixtures against Shrewsbury Town, FC Midtjylland and Arsenal would be pivotal in deciding whether or not Van Gaal kept his job at Old Trafford.
Thankfully for the Dutchman, though, he overcame that test, but last Thursday the gloom returned when his team were beaten 2-0 by their long-standing rivals at Anfield in the first leg of their Europa League last-16 tie.
Former United players Paul Scholes and Rio Ferdinand were heavily critical of the team, who managed just five shots at goal, only one of which was on target.
United will need to show more fight and desire when they host Liverpool on their patch, particularly as they need to score at least three goals to progress into the quarter-finals.
The Red Devils could be doomed should Liverpool score an away goal, but they have goalkeeper David de Gea at hand to keep them out and given that he made a handful of stops at Anfield, the Spaniard could prove to be pivotal.
The positive news for United is that they head into this match on the back of a much-improved display against West Ham United at the weekend.
Anthony Martial scored in the 83rd minute to seal a 1-1 draw against West Ham United in the quarter-finals of the FA Cup, meaning that a replay will take place at Upton Park at a later date.
Recent form: LWL
Recent form (all competitions): WWWLLD
Liverpool
Jurgen Klopp received an array of plaudits after guiding his Liverpool team to victory over Manchester United in the first leg of their Europa League tie last week.
The Merseyside outfit were quicker and sharper than their counterparts at Anfield and installed a gameplan that United struggled to match.
Liverpool were awarded a slice of luck with a 20-minute penalty, which Daniel Sturridge converted to give the Reds the lead, and after waves of pressure, Roberto Firmino doubled the team's advantage with a goal 73 minutes into the game.
Overall, the Merseyside outfit's spell under Klopp has been inconsistent since his arrival in October and, in a way, that was to be expected given that the former Borussia Dortmund boss needs time to shape his own team.
In the last few games, though, there have been signs of Klopp's influence, particularly as he has been able to welcome back injured players, including Sturridge and Philippe Coutinho.
Firmino is one member of the team who has begun to shine following a slow start to his career at Anfield. The Brazilian is the club's leading scorer this season with nine goals in all competitions, and three of those strikes came in the last three games.
As well as having a 2-0 lead in their favour ahead of Thursday's game, the Reds also have a decent European record to fall back on as they are unbeaten since February 2015 having won four and drawn five.
In addition, the Merseyside outfit have had a whole week to prepare for this game as they were not in action at the weekend.
Recent form: WWDDWW
Recent form (all competitions): DWLWWW
Team News
Bastian Schweinsteiger could be vying for a place in United's starting XI on Thursday after he made his return from injury off the substitutes' bench against West Ham.
Jesse Lingard could also return having missed the first leg at Anfield through suspension, but there will be no Wayne Rooney as the captain is not expected to be back in action until after the international break.
As for Liverpool, James Milner missed the first leg due to illness and he is currently serving a domestic ban, but he is eligible to feature this week.
Martin Skrtel made his return to the pitch after a lengthy spell out recently when he featured in an Under-21 fixture, but it will probably be too early for Klopp to throw him back into the first team.
Aside from long-term absentees Danny Ings and Joe Gomez, Liverpool have the majority of their senior players fit.
Manchester United possible starting lineup:
De Gea; Varela, Smalling, Blind, Rojo; Schweinsteiger, Schneiderlin; Mata, Lingard, Depay; Martial
Liverpool possible starting lineup:
Mignolet; Clyne, Lovren, Sakho, Moreno; Can, Henderson; Lallana, Coutinho, Firmino; Sturridge
Head To Head
Prior to last week's result, United had beaten Liverpool four times on the trot and they boast a positive home record having won 12 of their last 14 matches against their enemies in all competitions at Old Trafford.
Juan Mata may be struggling for form of late, but he has provided three goals and five assists in his last nine games against Liverpool.
For the Merseyside outfit, Sturridge has impressed against United having scored five and provided one assist in his last seven matches against them.
We say: Manchester United 2-1 Liverpool (2-3 on aggregate)
The pressure is on United to respond following the lacklustre display at Anfield and as mentioned, they need to score at least three goals to boot Liverpool out of the competition. Van Gaal's men showed against FC Midtjylland that they can excite on European nights and they will need the full backing of the Old Trafford faithful in order to do so. On the night, United are more than capable of winning the match, but Liverpool look dangerous on the attack and they could get that all-important away goal to send them through to the quarter-finals.