How psychological stress gets under the skin and contributes to increase the odds for the onset and progression of chronic diseases has been object of abundant research. In this literature review, evidence about the role that both acute (natural phenomenon, marital conflict, a social evaluative task) and chronic stress (stress at work, and the perception of being discriminated) as well as interpersonal stress have on physical health, is examined. Behavioral (lack of physical activity, smoking, lack of adherence) and physiological (dysregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, immune system and inflammatory response) mechanisms through which psychological stress may contribute to the onset and progression of cardiovascular disease (altering blood pressure, heart rate reactivity, hemoconcentration and pro-coagulation function), and two key processes involved in cancer progression (angiogenesis and metastasis) are discussed. Finally, how social support may moderate the association among psychological stress and physical health is described.