The issues of this dissertation is the process of return to work (RTW) that workers have to face after a long job absence due to a severe disease. This topic is relevant both at a social level, with the higher and higher cost due to disability and retirement, and at a personal level, with the positive effect on the quality of life of a reintegration in the working place. RTW is a multidimensional process influenced more by psychosocial determinants than traditional medical indicators. This dissertation conceives the RTW as a process that pass through several levels. From the decision to continue working during treatment to the struggles to remain employed once back at work. The studies exposed here address each of these phases considering RTW after cancer (CA) and cardiovascular diseases (CVD). The first chapter introduces the topic and present a recent approach to RTW that highlight the similarities of the process of RTW among different diseases in contrast to a traditional approach in which the studies are disease specific with no transfer of knowledge between them. In line with this, the first study is a review of published reviews aimed at identifying the factors affecting the RTW process that are common between different diseases. This review is unique because all the existing reviews are disease-specific instead this one explicitly searched for factors that are common. The study founded many common factors between the diseases considered: CVD, CA, and common mental disorder, but highlight many limits in the literature of the different diseases. The second chapter is about the RTW process after CA. This theme is explored with one longitudinal study aimed at finding the factors that influence the decision to continue working or stay at home during the cancer treatment and the factors that influence the probability and the length of the RTW after the cancer diagnosis. The first aim is scarcely analysed in the literature and the second is to our knowledge, the first study of this type in the Italian context. The results show the importance of motivational factors in influencing the decision of continuing the work activity during the CA treatment and the RTW process. Chapter three addresses the issue of the RTW after CVD with another longitudinal study that explored the changes in the working condition as perceived by the worker before and after the cardiac event and searched for the factors that affect the length and probability of RTW after CVD. Results show a significant decrease in the quality of the work experience after the RTW. Analysis revealed also that higher level of job strain and physical job demands before the cardiovascular event obstacle the RTW after CVD. The last chapter deals with the issue of job retention after RTW. We developed a new construct, the Work-Health Balance (WHB) and the WHB questionnaire that assesses the key factors in the process of adjustment between health needs and work demands, process that is fundamental in the phase that follow the RTW after a disease. The instrument developed shows good psychometric properties and significant correlation with several indicators of the quality of working life.