Apparent life-threatening events (ALTEs), because of their prevalence as well as their potential to hide serious diseases and consume significant medical resources, remain a challenge for physicians caring for infants. In this review, we focused on the assessment of the well-appearing infant for the most serious diagnoses, namely serious bacterial infections, seizure disorders, child abuse, metabolic disorders and severe apnoea with hypoxemia. Our extensive review of the literature has highlighted the difficulties physicians are facing in this evaluation, especially for the youngest infants (aged less than 2 months). Large-scale prospective studies are needed to identify risk factors and to guide physicians as to who should be investigated and the minimal investigation needed to avoid missing such conditions as serious bacterial infection, abusive head injury or repeated severe cardiorespiratory events. While infants with severe forms of metabolic disorders typically present with evident signs and symptoms, less severe forms of metabolic disorders, seizure disorders, and some forms of child abuse will often be diagnosed only when recurrent events are investigated.