The technological development increases flexibility and mobility and allows new ways of organizing work, such as telework. But, it is unclear how these changes are related to stress, health, and well-being among individual workers. Focusing on highly educated white-collar workers employed by the same organization, the aim of this work was to increase the understanding of psychophysiological activity in teleworking women and men and of positive psychological functioning, specifically psychological well-being and related physiological processes in effectively functioning, working individuals. The psychophysiological patterns of telework and the established linkages between psychological well-being and cortisol are related to existing models of work stress, health, and human functioning.