Matt Harmon was very determined not to let his physical disability get in the way of becoming a doctor. He was in a skiing accident when he was 18, which left him in a wheelchair. One of the most compassionate interns, he has tried to help others through their problems. Unlike the other interns, he managed to strike up a friendship with the hard-nosed Ellen Burgess. Romance took several months. In the meantime, he dated nurse Grace Sullivan, who went on the run with him when brother Bobby Mancusi learned his location and tried to kill him. Matt had joined the witness protection program to get away from his family. Matt killed his brother in a gun battle, and his father Salvatore called a truce.

Matt helped Ellen deal with her family crises, their barriers broke down (she was reluctant to be involved with someone she supervised), and they made love. Even after Chris Ramsey exposed their relationship on the bulletin board and Ellen was removed from supervising the interns, their love stayed strong.

Matt wanted to be on the surgical rotation, but arrogant chief of surgery Dr. Boardman refused to let him participate, because of his paralysis. When Matt successfully operated on Boardman after a knife attack, Boardman changed his mind.

In 1999, a dying man from Ellen's past came up, named Sebastian and pushed Ellen and Matt further apart. Sebastian quickly died and Matt and Ellen continued their relationship, until Matt learned Ellen had slept with Sebastian to fulfill his last wishes. Matt broke up with her. When he began to change his mind, Ellen had vanished, supposedly taking a job in another town. Kevin and Matt tried repeatedly to track her down, but she was nowhere to be found. Matt then spent a long time on the backburner.

In April of 2000, Matt was able to walk for the first time in years thanks to Para-Step walker technology. A few days later, card buddy Frank was shot. His gambling debts were the initial cause most suspected, but soon Mac told Matt that it was a botched attempt on Matt's life because of his ties to the Mancusi crime family. Matt agreed to enter the Witness Protection Program, and left Port Charles for good.