The treatment of chronic disease is often complicated by the coexistence of multiple medical conditions and by the presence of social and psychological impediments. The needs posed by patients with chronic disease are overwhelming the capacity of the American health care system. Alternative disease management systems that rely on specially trained nurse case managers to implement detailed clinical protocols, including drug algorithms, have shown efficacy in managing chronic medical conditions, singly and in combination. By fostering integration of care across subspecialty and medical-social boundaries, such systems enable treatment of the patient with disease(s), not simply treatment of disease(s) in the patient. Working closely with primary care physicians, often by telephone-mediated interaction with patients, nurse case managers may take an expanded role in meeting the challenges posed by chronic disease.