This chapter addresses the most common risk factors increasing maternal and offspring health disadvantages. Psychosocial vulnerability, including maternal stress and substance abuse, overweight and obesity, psychiatric disorders, chronic and acute infections, autoimmunity, chronic kidney disease and hypertension, cardiac disorders, either acquired or congenital, and diabetes mellitus are systematically evaluated on the effect of the condition on pregnancy and vice versa, and the possible effect of specific disease-modifying drugs.