Ryan Bingham works for a human resources consultancy firm specializing in termination assistance. His work constantly takes him around the country, conducting company layoffs on behalf of employers. Ryan also gives motivational speeches, using the analogy, “What’s in Your Backpack?” to extol living free of burdensome relationships and material possessions. A frequent flyer, Ryan aspires to earn ten million frequent flyer miles with American Airlines. While traveling, Ryan meets Alex, a professional woman who also flies frequently. They begin a casual relationship, meeting up in various cities as schedules allow.
Ryan is recalled to his company’s offices in Omaha, Nebraska. Natalie Keener, a young, ambitious new hire, promotes cutting costs by conducting layoffs via videoconferencing. Ryan, unwilling to give up traveling, raises concerns that the new system could be impersonal and apathetic, and argues that Natalie lacks understanding about the firing process and how to handle emotionally vulnerable people. Ryan’s boss, Craig, has Natalie accompany Ryan on his next round of terminations to observe the process.
Ryan tutors Natalie on traveling more efficiently using smaller luggage and moving quickly through airport security. As they travel together, Natalie questions Ryan’s philosophies on life, particularly regarding relationships and love, but Ryan defends his lifestyle. During the trip, Natalie’s boyfriend unceremoniously dumps her by text message. Natalie, shattered, is comforted by Ryan and Alex. On a video termination test run, Ryan’s earlier concerns prove valid; when one laid-off person breaks down on camera, Natalie is unable to properly console him. Another employee threatens suicide.
Natalie later castigates Ryan for refusing to commit to Alex, despite their obvious compatibility. In turn, Ryan criticizes Natalie for lacking empathy and never appreciating her surroundings. Soon after, they are ordered back to Omaha to implement Natalie’s program. Before returning home, Ryan, taking Alex along, heads to Wisconsin for his sister, Julie’s wedding. He has a strained reunion with his semi-estranged family who resent his absence. When Jim, the groom, gets cold feet, Ryan’s older sister, Kara, asks Ryan to use his motivational skills to persuade Jim to proceed with the wedding. Although this runs counter to Ryan’s personal philosophy, he successfully argues that life’s most important moments are ones shared with others. The wedding proceeds without any further hitches.
Ryan begins questioning his lifestyle and philosophies, and doubts what he lectures others about. Ryan has strong feelings for Alex and impulsively flies to Chicago. Arriving at her home, he is stunned that she is married and has children. She later phones him, saying that her family is her real life; he is merely an escape.
On Ryan’s flight home, the crew announces that he has just crossed the ten million mile mark. American Airline’s chief pilot is aboard to personally congratulate Ryan and notes he is the youngest person to achieve the milestone. Back in Omaha, Ryan transfers flyer miles to Julie and Jim so they can have a honeymoon. Ryan’s boss informs him that a woman he and Natalie laid off has killed herself. Natalie, upset, has quit via text message. The remote-layoff program is put on hold and Ryan goes back on the road.
Natalie applies to the same San Francisco company where she previously declined a position. She admits she followed her now ex-boyfriend to Omaha. The interviewer hires her, impressed by her qualifications and Ryan’s glowing recommendation. The film concludes with Ryan standing in front of a vast destination board, looking up, and letting go of his luggage.