Most established risk factors for chronic disease incidence and mortality from cancer, such as cigarette smoke, alcohol drinking, occupational and environmental hazards and dietary factors, have been shown to vary in their importance in terms of relative risk. In studies which addressed the individual level of behaviour, but also coping and self-regulation, a strong modifying effect of long-lasting hopelessness and helplessness has been found to depend on personality. Autonomy and healthful self-regulation have been defined as the regulation of behaviour in those activities which are carried out in the physical and social environment and lead to stimulated feeling, pleasure, perception of inner and social security, and competence. Persons with such well-regulated behaviour are capable of coping with sources of listlessness, uncertainty and instability. Those individuals showing a well-regulated behaviour arrive at a psycho-neuro-physiological basis for better competence and defence against health hazards. The capability determined by the degree of self-regulation is measured with different instruments. The experience with a questionnaire for the assessment of self-regulation, its quantification and predictive value is presented here. The method of study is by prospective approach, which permits the demonstration of causal associations (promotion, co-causality) and facilitates the experimental approach through intervention. A causal association is likely if the effect of a modifier is not only found in a prospective (observational) follow-up but also if the (experimental) intervention shows an effect. The method of intervention by stimulation of self-regulation is the autonomy training developed by Grossarth-Maticek. Using several examples presenting the method, the modifying effect is shown by referring to four risk factors. If the risk factors are associated with an inhibited self-regulation, then the effect in terms of disease and pathological outcome is stronger. This was shown with the hazardous effects of smoking, alcohol drinking and dietary malnutrition as well as with automobile exhaust. It may be important, for example, whether a person feels self-determined when driving a car for hours but does not need to consume ethanol-containing drinks for feeling well. One's own capability to regulate well over time apparently modulates functions of the body and hence modifies the effects of physical factors. In epidemiological studies, which assess mostly only exogenous factors (so called established risk factors) this evidence has to be considered by including the pertinent data on the relevant questions in each field study.