Psychosomatic medicine can be seen as a comprehensive framework for a holistic consideration of patient care that encompasses the interaction between psychosocial factors and biological factors in the predisposition, precipitation, perpetuation, and the patient’s coping with disease or health state. In this multifactorial frame of reference, the roles of stressful life events, allostatic load, and health-damaging behavior have provided an opportunity for prevention efforts in a holistic manner. This chapter gives a brief historical background of psychosomatic medicine in general and specifically in Africa. There are variations in the literature and experiences in different aspects of psychosomatic medicine. Cultural differences may explain these variations. One of the differences lies in individualistic and collectivistic cultures. Although no single society will conform to a single stereotype and that, in reality, a continuum exists between the two, in a tabular form, we look at the influences of cultural differences by carrying out a SWOT (strengths, weaknesses, opportunities, and threats) analysis in regard to the occurrence of psychopathology, course of illness, and prevention. This chapter is concluded with clinical implications.