Joe Scanlon was a determined and compassionate young doctor. Growing up, his family faced hard times, and he had mixed feelings about leaving home to pursue his dream of becoming a doctor. Joe and Frank had a turbulent relationship, since Frank helped pay for Joe's medical school, and took their father's beatings. Joe always resented being the forever-grateful "little brother." Eventually, they mended fences.

He came home to Port Charles to become an intern at General Hospital. He had boundless compassion for his patients, but even more feelings are shown for his old childhood friend, Karen Wexler Cates.

Not long into their relationship, Joe's old flame Courtney Kanelos returned to town. Her son, Neil, was dying of leukemia. Joe put the pieces together and Courtney admitted Neil was his. Neil was actually Frank's, but over a year passed before Joe learned the truth. Courtney was obsessed with winning Joe back.

Karen and Joe were engaged to be married, but Karen called it off when she believed he was a sex addict, he really wasn't, his brother, Frank and former girl friend, Courtney were setting him up. However, Karen and Joe realized Frank was framing him and they reunited. Joe and Karen got into a huge fight over her not telling him that Frank was Neil's father, and over the best treatment for Neil. Her knowing he wasn't Neil's father weeks before he did led to a breakup, but after some initial hostility, they remained friends.

Joe took a tougher stance on life, standing up to Frank, violating medical procedure to give Neil an untested treatment for leukemia (which worked, but got him suspended for a period of months), and carrying on with women. A night with a nurse, Jill, led to unforeseen consequences. After she found out she was HIV-positive and told Joe, he had to go through HIV tests for over a year. At this time he had fallen in love with sweet, pure nurse Gabriela Garza, who patiently waited until the time they could become intimate.

Courtney, who wanted Joe away from Neil because of the HIV, leaked to reporters that an HIV-positive doctor was on staff. After some plotting from Gaby, Joe, and Frank, Courtney's misdeeds were exposed.

Joe and Gabriela had a stable, happy several months, and got engaged. They planned to move to Appalachia, working in a clinic together. In summer 2001, his last HIV test came back negative, indicating it was safe to make love. Their first time was wild and rough, due to Gaby being bitten and enthralled by vampire Caleb. Shortly thereafter she dumped him altogether for her "mystery man." When Joe tried to get through to Gaby, she became physically violent. Brokenhearted from the broken engagement, Joe left town, eliciting a promise from Frank and Karen to look after Gaby.

Joe returned in February 2002 when Gabriela was seriously injured in a fall. She had recovered from her vampire-thrall period, and was back to her old self. Putting the past behind them, Joe asked Gaby to come live with Appalachia with him, and she happily accepted. After a surprise goodbye party thrown by Joe's family, Joe and Gaby left town to live happily ever after.