Conjugal bereavement, which is considered as one of the most intense psychosocial stressors, has been studied extensively for the last three decades. However, despite the wealth of data indicating the deleterious consequences of the death of a spouse, the process by which bereavement is translated into ill health and increased mortality remains unclear. Prior research has shown that not all individuals undergoing conjugal bereavement are equally affected. Increased morbidity is more likely to be observed in the young-old group, and those who are not able to cope with grief adaptively. A careful examination of the literature identifies two major issues that have not yet been addressed adequately. The first relates to the elusive physiological mechanisms underlying bereavement-induced morbidity. The second concerns the exclusive focus on vulnerability in prior research, which results in a lack of understanding of the factors facilitating better adjustment. This paper addresses the two issues, and puts forward a psychoneuroendocrine model to inform future research.