Lady Macbeth has killed herself, Macbeth's people have abandoned him, he is considered a tyrant, and he is forced to kill many soldiers during a battle, and through these actions, he realizes how pointless it was. He becomes disillusioned with the idea of working so hard and betraying so many to become a king that no one respects, only to die some day, rendering all his efforts meaningless and going to his grave unwept and unsung.
Suddenly, "Life is a tale told by an idiot; full of sound and fury, signifying nothing" has an even stronger impact.
Macduff, when he learns that his family has been killed. The worst part is when he keeps asking, bewildered and lost, 'My children too? My wife too? All of them?'
All my pretty ones? Did you say all?
One production had Macduff staring in sheer disbelief and shock, then laughing when Malcolm says they'll get revenge, spitting back "He has no children." Then all at once he fell to his hands and knees and screamed, again and again.