The Safin siblings surged through the Australian Open draw on Wednesday, women's third seed Dinara and men's former world number one Marat sliding into round three.
Big brother Safin thundered through to a mouth-watering showdown with second seed Roger Federer after he crushed Guillermo Garcia-Lopez 7-5, 6-2, 6-2, while Safina, chasing her maiden Grand Slam title, beat fellow Russian Ekaterina Makarova 6-7, 6-3, 6-0.
Federer stormed to a 6-2, 6-3, 6-1 victory over Russia's Evgeny Korolev.
Twice runner-up here and champion in 2005, Safin is eagerly anticipating his clash with the 13-times Grand Slam champion.
"I'm looking forward. I have nothing to worry about. I'm going to play my match," said Safin, who beat the Swiss the last time they faced off at the Open in the 2005 semis.
"We know each other pretty well. He knows how to play against me, I know how to play against him.
"Unfortunately I didn't win a lot of matches against him, but I'm looking forward. It's another chance. I have nothing to lose. I'm going to go for it. Whatever comes, comes."
Federer was equally keen to clash, even though he holds a commanding 9-2 lead in their head-to-heads.
"It's going to be a nice match for sure," he said. "We have a history. We have played a few times.
"We've played in majors before and played some good matches before... We go way back.
"Him, of course, being a former number one, same for me, former Grand Slam champion, it's an intriguing matchup."
Federer and Safin were joined in the winners' circle by the Serbian trio of Jelena Jankovic, Ana Ivanovic and defending men's champion Novak Djokovic. Andy Roddick also progressed.
Women's top seed Jankovic beat Kirsten Flipkens 6-4, 7-5 and fifth-seeded Ivanovic beat Italy's Alberta Brianti 6-3, 6-2.
"She's not an easy opponent. She can be very dangerous," Ivanovic said of her performance against Brianti.
"There is still some areas I have to work on and improve.
"I know there is still lots of room for improvement. So that gives me confidence," added the 21-year-old, a beaten finalist at Melbourne Park last year.
Djokovic eased into the third round with a 7-5, 6-1, 6-3 win over France's Jeremy Chardy.
The 21-year-old world number three struggled initially against Chardy in an even first set, breaking just once in the 12th game, before he romped away with the second and third.
"I'm playing better and better which is a very encouraging fact for me," Djokovic said. "I really stepped it up and played pretty good in the second and third set especially."
Roddick, the last American man to win a Grand Slam title with his 2003 US Open crown, ousted Belgian qualifier Xavier Malisse 4-6, 6-2, 7-6, 6-2.
"I felt good from the first ball," Roddick said. "Credit to him. He came out with a good game plan and he was just going to fire."
Argentina's David Nalbandian had no excuses for becoming the highest ranked men's player to be knocked out.
"I don't think I played bad, but every set I was starting a break down and had to fight from a break down and come back," the 10th seed told reporters after he was beaten 6-4, 5-7, 4-6, 6-4, 6-2 by Taiwan's Lu Yen-hsun in the second-round.
"He played, I don't know if it was perfect, but he played at a very good level."
The host nation suffered mixed fortunes in the night session on Rod Laver Arena.
Australia's next big hope, 16-year-old Bernard Tomic, was brought down to earth with a 3-6, 6-1, 6-4, 6-2 defeat by Luxembourg's Gilles Muller.
Former world number four Jelena Dokovic thrilled a seething mass of green and gold local fans by beating Russian 17th seed Anna Chakvetadze 6-4, 6-7, 6-3.
"I've just been really, really focused and really wanted it so bad," the on-again-off-again-on-again Australian said.
"Things are going really well at the moment."