For England, it will be Manu Tuilagi. The Leicester powerhouse became a major attacking weapon for Stuart Lancaster's side, and England are way less dangerous without him.
For Wales, the skills of Jonathan Davies will leave a hole that young Scott Williams will have a tough job to fill.
Ireland will not be the same side without Sean O'Brien's muscularity in defence and attack.
France will be missing the finishing power of Vincent Clerc on the wing and the cool head and accurate goal-kicking of Morgan Parra.
Scotland will miss Richie Gray if he plays and is below his best. They need the big man firing on all cylinders.
Italy will miss a decent fly-half. Luciano Orquera showed flashes of excellence last season, but they need a general at No. 10.