SIMON TAM is the medic aboard Serenity. A former trauma surgeon in Capital City on Osiris who graduated in the top three percent of his class and finished his internship in only eight months, Simon had paid men to smuggle his sister River out of a government sponsored academy where she was the subject of inhuman experiments. He had booked passage aboard Serenity to take him and the cryo container containing River to Boros, however an Alliance mole named Lawrence Dobson revealed to the crew that Simon was a fugitive. Captain Reynolds opened River's stasis module, and Simon explained to the crew that his sister was a genius and he had spent the last four years desperate to free her. After Dobson shot Kaylee, and tried to kidnap River on Whitefall, Captain Reynolds shot the fed and offered Simon a position as ship's medic, as well as offering a safe place for both him and River.

River is Simon's entire world. He has dedicated himself to trying to find some treatment for her condition. Because he adores his sister, he can be selectively blind where she is concerned, insisting that she's merely intuitive when others observe that River appears to have the ability to read minds. A serious young man, he can get quite snarky if he's frustrated. However, on the whole, Simon retains the good manners and breeding of a young gentleman of the Core, which at times frustrates the more laid-back Kaylee. His accounts were crashed when he kidnapped River, so he literally has nothing remaining of his old life but the clothes off his back, his medkit, and his sense of propriety.

Despite a rocky start with the captain (who punched Simon out twice the first day they met), Simon slowly settles into life aboard and begins forming tentative bonds with the other crew and passengers. The crew even throw him a birthday party when a fresh warrant for his arrest, complete with birthdate, appears on the cortex. Simon is closest to Kaylee, who has made the young doctor her personal mission. He has a very adversarial relationship with Jayne, who delights in insulting and playing cruel practical jokes on him. Simon was extremely grateful for Jayne helping him and River to escape from St. Lucy's on Ariel, and Jayne accepts his hero-worship grudgingly. However, Simon does not yet know that Jayne tried to turn him and River over to the Alliance on Ariel, and is therefore indirectly responsible for a bounty hunter named Jubel Early being sent after Serenity to retrieve River for the mysterious Blue Hand Group.

Simon can handle a gun, but has yet to actually bring himself to kill. He helped as best he could during the assault on Niska's skyplex, and will do anything to protect his sister, but as a doctor, his first instinct is to save lives rather than take them. Simon gets kicked around a lot--and Kaylee rides him for not fighting back. However, he didn't hesitate to attack both Dobson and Jubel Early, when they tried to take River. At first very reserved and "stiff", he has loosened up considerably, particularly around Kaylee, sharing with her drunken Medacad exploits and genuinely enjoying her company. While he may not be able to express his affection as easily as she might like, he does appear to have genuine feelings for her.