The digitalization of work, accelerated by the COVID-19 pandemic, has transformed home-based work into a widespread reality. Initially gradual, this shift intensified abruptly, requiring employees to develop digital competencies and self-management skills rapidly. This book chapter explores the ergonomic and health-related implications of this transition, beginning with a conceptual differentiation between stress, stressors, and job demands. It then examines the specific ergonomic demands of remote work across three domains: physical (e.g., environment, furniture), organizational (e.g., boundary management, self-organization), and cognitive (e.g., multitasking, technostress). An integrated perspective frames these demands as part of a continuous regulation process across three central domains of individual functioning: work-life balance, health behavior, and performance behavior. The analysis extends to health-related outcomes, including changes in eating behavior, physical activity, and musculoskeletal health. To further examine the health impact of these demands, data on musculoskeletal pain and sleep from 1305 participants of the 2022 Swiss Job-Stress-Index questionnaire study were regressed on the ergonomic demands of remote work and onsite work to test their unique risk potential. Results show unique risks with slight differences concerning health outcomes and participants’ gender. The interaction between remote work ergonomics and onsite work ergonomics confirms that good work design at both workplaces is more health-protective than would be expected from mere additive design effects. Occupational health prevention should focus on both work domains and improve the ergonomics of remote work, especially for women.