The increasing discrepancy between the donor hearts available and the number of patients with advanced heart failure underscores the need to optimize medical therapy and restrict the option of cardiac transplantation to patients with heart failure refractory to maximal conventional therapy. New medical and surgical therapies should be studied specifically in this population. The need for heart transplantation in ambulatory patients with severe heart failure is better assessed by the serial evaluation of objective measures of clinical stability and peak exercise oxygen consumption, than by assessment of standard risk factors at the time of patient referral. Among comorbidities which may preclude transplantation, psychosocial risk factors have recently undergone stricter scrutiny. The successful outcome of candidates for heart transplantation requires serial assessment and continuity of care by a dedicated team of health professionals specialized in heart failure and transplantation.