Occupational Contact Dermatitis (OCD) is one of the most common work-related diseases. High risk occupations are in health care, hairdressing, food sector and metal industry. OCD tends to become chronic; persistent OCD often results in impaired quality of life and loss of work ability. The purpose of this article is to review the present knowledge on the factors which determine individual susceptibility to acquire OCD. Recent discoveries regarding genes involved in the skin barrier, inflammatory response and biotransformation of xenobiotics provide more insight in the individual susceptibility for OCD. Knowledge of the factors which predispose to OCD is useful in occupational health practice for the application of preventive measures and for career guidance for apprentices and workers in high risk occupations.