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When the sequence begins, in December 2000, Nate is returning home from Seattle to rejoice Christmas with his family. Nate had deserted the family business years earlier. After graduating from Bonaventure High School and presence U.C. Santa Cruz, Nate traveled through Europe and later established in Washington State, where he managed the main organic food co-op in Seattle. However, following his father dies, Nate delays returning to Seattle for a small number of days, which end up growing into a few years. He and David each come into half of their father's business, Fisher & Sons, and Nate ends up sticking approximately to help run the business after he comes to realize that he has a natural gift for reassuring people in their time of grief. He also develops a relationship with Brenda Chenowith which begins as a random sexual meet in an airport and slowly becomes something more.
In July 2001 (the opening of the second season), Nate learns that he has arteriovenous malformation (AVM), a potentially fatal mind condition which could cause him to have a seizure or caress at any time. Nate has a very marked fear of death, causing him to initially hide the information from each one around him in order to avoid admitting his very real chance of dying youthful to himself. Early in the season, he visits Seattle and seeks soothe from Lisa Kimmel, his "fuck-buddy" during much of his time there. He ends up cheating on Brenda with her, only adding to the subliminal pressure on him; worse, he has his first seizure while there. Additionally, more than a few months after leaving Seattle, Lisa moves to Los Angeles and Nate learns that she is pregnant. Through the course of the period, however, Nate slowly becomes able to face his fear, and finally is able to tell his family concerning the condition and seek a high-risk surgical procedure as treatment for it; he is also able to tell Brenda about impregnating Lisa, but when it turns out that she had been cheating on him as healthy, they split up. The season ends on a cliffhanger, with Nate undergoing the high-risk surgical process required to save his life.
The third season begins on a surreal note, exploring a variety of possible outcomes of Nate's surgery and his life, and then skips in front in time to late 2002, where it is exposed that Nate and Lisa have gotten married; their daughter, Maya, is three months old. Their relationship, however, is tumultuous, and just when things are opening to look up for the couple, Lisa is reported absent, and a month later her drowned corpse is found. Nate is forced to deal with together Lisa's death and being a single parent for Maya for a time, but finally he rekindles his relationship with Brenda, and the two become engaged for a second time, marrying six months afterward, in October 2004 (the opening of the fifth and final season). Their wedding day, though, is darkened by Brenda's miscarriage the previous day.
Brenda afterward becomes pregnant again, but she and Nate disagree on whether or not she ought to get an abortion if the child has special needs. Nate establishes solace from his troubles in his sister-in-law Maggie Sibley and the Quaker religion, and the two finally have sex. Immediately afterwards, Nate suffered a brain blood loss from a second AVM that has urbanized since his mid-2002 surgery, and slips into a brief coma. He wakes up in the hospital the next day, and the doctors consider he will have a healthy revival over the next few weeks. Brenda tells him that she forgives him for his infidelity, but he responds by saying that he needs a divorce. Nate is also visited by David, Claire, Rico, and Maggie, but Ruth can't be reached owed to being away on a camping trip. At the end of the day, Nate without warning and abruptly dies in his hospital bed, while David is sleeping at his side.
Following his death, the sequence spends several episodes on the other characters' lives as they effort to cope with his absence. Nate appears more than a few times to them as a representation of their own thoughts, in a tool that had been commonly used for many dead characters all through the series to dramatically illustrate characters' internal monologues. When Ruth dies 20 years afterward, the last thing she sees is Nate.