The FIFA Ballon d'Or winner, who scored a competition-record nine goals in the group stage, returns after serving a three-match suspension in La Liga for his sending-off against Athletic Bilbao earlier this month.
Ronaldo's availability is a further boost in confidence for the Spanish giants, who travel to the Veltins Arena in hugely impressive form.
The nine-time European champions are unbeaten in 27 games in all competitions, of which they have won 23.
Carlo Ancelotti's men have also kept 13 clean sheets in their last 15 games, helping them through to the final of the Copa del Rey and to open up a three-point lead over Barcelona and Atletico Madrid at the top of the Primera Division standings.
"We are where we want to be," Real captain Iker Casillas said to www.marca.com. "We are alive in three competitions and we are fighting to win them all.
"We know it's going to be difficult to win a treble but we will try.
"The team is playing well and we are going through a good spell.
"We are giving away few goals while we are solid in attack."
Casillas knows his team must keep their feet firmly on the ground though, warning Schalke pose a serious threat to their dreams of winning a record 10th European Cup title this season.
"We are looking forward to Wednesday's match," the Spain goalkeeper said. "Every player would want to play such an important game.
"Schalke are incredibly strong physically and they are consolidating a top four spot in the Bundesliga.
"I consider them a dangerous rival.
"We will have to try to limit the advances of (former Real Madrid striker) Klaas Jan Huntelaar, who could make life difficult for our defenders."
Huntelaar, who played for Madrid six years ago, insists his side are underdogs for the tie but will be hoping they can get a good result on Wednesday night to take to the Bernabeu for the return leg on March 18.
"Madrid are favourites," Huntelaar said to www.marca.com. "But we are playing the first leg at home and we will make them work very hard.
"Our fans are really excited about this game, which will be a spectacular one.
"This is the first time we face Madrid and we will try everything to beat them and continue in the competition."
Jens Keller's side are unbeaten in the Bundesliga since December 7 and last Friday's goalless draw against Mainz was the first time in 2014 that the club have failed to record a win.
That run has left them fourth in the standings, one point adrift of third-placed Borussia Dortmund and two adrift of Bayer Leverkusen in second.