The literature indicates that cognitive appraisals and illness-related beliefs are key cognitive factors that affect the outcome of psychological adaptation to chronic illness. The main aim of the current study was to identify which cognitive appraisals and illness-related beliefs are the best predictors of adaptation to living with chronic illness as well as which of these predictors are universal, and which are illness-specific. Data was collected online from 505 panel study participants who reported diagnoses of rheumatoid arthritis, asthma, hypothyroidism, diabetes, and hypertension. Adaptation indicators (i.e., depressive symptoms and level of acceptance of living with the illness) differed significantly across samples with different medical diagnoses. Additionally, illness-related cognitive appraisals, but not illness-related beliefs, had a statistically significant specific contribution to explaining the variance in adaptation indicators. The predictors of adaptation to living with chronic illness differ between the diagnoses and the adaptation indicators. The results can contribute to a better matching of therapeutic interventions as well as social campaigns aimed at people suffering from chronic illnesses.