Psychosocial support, education and self-management are important complements of rehabilitation programs. A central concept in self-management is self-efficacy, which refers to oneself confidence in reaching a desired goal. The General Perceived Self-Efficacy scale (GSE), developed to measure self-efficacy at the broadest level, could be useful in the rehabilitation setting, in order to assess patients' self-management difficulties as well as to design specific interventions for specific diseases. Aim of this work is to verify the GSE Italian version psychometric properties applied to the rehabilitation setting. Data were analyzed from 395 in-patients attending cardiac (83.8%) and neurological (16.2%) rehabilitation. Cardiac patients suffered from post-MI, CABG or heart-failure; all of the neurological patients suffered from amiotrophic lateral sclerosis (ALS). They were mostly males (84.5%), and the mean age was 55.7 years. Principal component factor analysis confirmed that GSE has a monofactorial structure with internal consistency of .85. As in previous studies, a gender difference emerged. There was no difference in cardiac patients, on the basis of their specific disease, but they showed higher self-efficacy perception compared to ALS patients. The findings confirm that GSE is a valid measure of self-efficacy in settings characterised by different levels of functional abilities, as in cardiac and neurological rehabilitation.