The increase of chronic diseases worldwide impact quality of life, cause economic and medical costs, and make it necessary to look for strategies and solutions that allow people with chronic diseases (PwCDs) to lead an active working life. As part of the CHRODIS Plus Joint European Action project, a systematic review was conducted to identify studies of interventions that support the maintenance of work and return to work (RTW) among workers with chronic illnesses. These interventions should target employees with the following conditions: diabetes, cardiovascular diseases, metabolic vascular syndrome, respiratory diseases, musculoskeletal disorders, mental disorders, and neurological disorders. An extensive search was performed in PubMed, EMBASE, and PsycINFO for English language studies. Included in this review were 15 randomized controlled trials (RCT) for adult employees (aged 18+). We found that workplace-oriented and multidisciplinary programs are the most supportive to RTW and reducing the absence due to illness. In addition, cognitive behavioral therapies achieve positive results on RTW and sick leave. Finally, coaching is effective for the self-management of chronic disease and significantly improved perceptions of working capacity and fatigue.