The working environment may have a significant effect on response to treatment of depression and this issue has not yet been sufficiently addressed in the scientific literature. There is evidence showing that being engaged in high-level positions can be an obstacle to the success of treatment. This article discusses the few evidence in the literature and some of the possible mechanisms involved. Specific personality attributes and difficulties in adapting to depression may delay access to care and may also reduce treatment compliance. The presence of stress in jobs that require high cognitive function and lack of social support may be elements that hinder the recovery process. Residual symptoms that impact on cognitive functions may undermine adherence to treatment and adversely affect the response. The implications of these issues are potentially relevant for clinical practice in the treatment of depression and for future research.