Previous research has established the physical and mental benefits of using active workstations like treadmill desks in the workplace, such as reducing sedentary behavior and improving mood. However, treadmill desk use when working at home has not been examined despite significant increases in working from home during the COVID-19 pandemic. Therefore, the objectives of this study were (1) to be the first to describe how treadmill desks are used when working from home and (2) to identify specific factors that are motivators or barriers for treadmill desk use when working from home. Twenty participants who worked from home and used a treadmill desk were interviewed between February 2022 and April 2022. Participants reported using their treadmill desks while completing a variety of work and non-work tasks and experienced positive physical, mental, social, and work-related outcomes. Motivators for use included desires to be healthier and fitter, tracking and reaching goals like daily step counts, feeling good during and after use, and to overcome increased sedentary behavior due to working from home during the COVID-19 pandemic. Barriers to use included the type of work being done, physical limitations, accessibility issues, social concerns, and mental barriers such as boredom. Future research should investigate ways to increase treadmill desk use at home by capitalizing on motivating factors and reducing barriers to use.