In the present study it was empirically explored how work-situation dimensions, personality dimensions, and personality-by-situation interactions are related to burnout and general mental ill health. Questionnaire data from 694 subjects were analyzed using hierarchical multiple linear regression analyses. The results suggest that: (a) personality should not be disregarded in theoretical discussions and empirical studies of burnout and general mental ill health; (b) personality can, to some extent, condition how the work environment dimensions affect an individual with regard to various aspects of burnout and general mental ill health; (c) attention should be given to the fact that some measures of burnout and mental ill health are more dependent on situational factors while other measures are more dependent on personality factors.