Cancer is the second leading cause of death in the United States, and the majority of hospital admissions of patients with cancer occur because of uncontrolled, urgent symptoms. In addition to complex physical presentations, these patients often manifest a number of complex emotional and psychological responses resulting in a unique set of healthcare needs and expectations. Inpatient generalists or hospitalists frequently serve as the primary providers of medical care for these patients. Formal training for nononcologists on effective communication strategies in managing patients with cancer in a hospital setting may not fully prepare generalists for challenging patient encounters, however. This review assists generalists in approaching emotionally charged encounters when caring for patients with cancer on the wards. We explore patient factors that negatively affect successful communication, some of which can be addressed through a multidisciplinary approach. In addition, we present a checklist of preventive strategies in addressing emotionally charged patient responses and offer a number of preventive and restorative management approaches for dealing with such encounters. We provide a practical framework for recognition and management of the psychosocial and emotional challenges in the care of hospitalized patients with cancer.