The will to live is a natural instinct experienced by all human beings. It tends to persist in humans, despite marked adversity such as that associated with advanced cancer. The will to live may be measured directly, or indirectly, by assessing the desire for hastened death. Factors that may affect it include age, life stage, and physical and psychological distress. In particular, states of depression and hopelessness may precede the loss of the will to live. Other psychosocial variables that may affect the will to live include physical suffering, attachment security, self-esteem, and spiritual well-being. A number of screening tools are available to identify risk factors for the loss of the will to live. Awareness of these factors can guide interventions to preserve morale and maintain hope in patients faced with a terminal illness. Critical among these are the alleviation of physical and psychosocial distress and the establishment of a therapeutic alliance that is sensitive to the specific support needs of individual patients. Comfort and facility with such supportive interventions in oncology will require greater attention to the development of communication and relationship skills at both undergraduate and postgraduate levels of training.