Aim Floppy infant or congenital hypotonia indicate decreased muscle tone in infants due to abnormalities either of central nervous system, peripheral nervous system, or both. Previous literature classified the causes to be of central versus peripheral origin, however, recent study addressed new classification of combined origin, and hereby we follow the new version of etiologic classification. We aim to review the most common etiology according to the age of presentation. We also review clinical characteristics, resultant diagnoses and developmental outcome of these populations. Method Total 116 patients were retrospectively recruited from the electronic medical chart, whom were diagnosed with either floppy infantile syndrome or congenital hypotonia from January 2005 to December 2016 at Severance Children’s Hospital. Among them, 66 subjects with confirmative diagnosis were reviewed for the etiologic classification. We reviewed clinical information including birth history, presenting symptoms and diagnosis, and also obtained phone interview from each subjects’ families for developmental outcome. Results The new etiologic classification revealed 34 patients (51.5%) of central origin, 21 patients (31.8%) of peripheral origin and 11 patients (16.7%) of combined origin, respectively, from 66 patients with confirmative diagnosis. On the other hand, among 50 patients without confirmative diagnosis, 10 patients (20.0%) had mild abnormality in brain imaging and 10 (20.0%) patients had mild global developmental delay with no apparent abnormal diagnostic findings, respectively. Prader-Willi syndrome (34.6%) and myotonic dystrophy (19.2%) were the 2 most common causes in neonates, while spinal muscular atrophy (20.7%) was most frequent in the subjects presented during age 1-12 months. Mitochondrial myopathy was notably common in our study population due to presence of mitochondrial disease clinic at our institute. We also evaluated developmental outcome in terms of cognition, language, motor, respiration and feeding. Conclusion We proposed the importance of systematic evaluation of etiologic diagnosis and timely application of new genetic technologies and genetic counseling. Long-term prospective regular checkup of developmental outcome is necessary for the optimal care management and improved quality of life for the patients and families.