Since you categorized this question under literature, I'm assuming that you are writing a paper about the theme of guilt in literature. A determining factor in how you approach this is deciding on a corpus of works to cover. You can either look at the nature of guilt within a specific corpus of literary works or you can compare and contrast how guilt is handled in different literary traditions. Some possible themes would be:

• Guilt versus shame cultures: One can argue that pre-Christian western works such as Homer's Iliad reflect a shame culture and works set in a Christian environment such as Shakespeare's Macbeth and Fyodor Dostoyevsky's Crime and Punishment reflect a guilt culture. One could investigate the theme of literary portraits of guilt versus shame cultures.
• The Furies and the other Greek gods externalize guilt in many Greek dramas. You might look at themes of guilt in the Oresteia or the Theban plays of Sophocles and discuss it in relationship to the gods. 
• In modern literature, guilt is sometimes portrayed as punishing people by driving them insane. You could choose works such as Macbeth (focusing on Lady Macbeth) and Edgar Allen Poe's "The Tell-Tale Heart" to exemplify the theme of the relationship between guilt and insanity.