The diagnosis of a pustular dermatosis occurring during the first months of life is usually based on clinical findings. However, some cases may require simple investigations including microscopic examination of pustular content, cultures, and skin biopsies. The main benign transient neonatal types of pustulosis include erythema toxicum neonatorum, infantile acropustulosis, transient neonatal pustular melanosis, and neonatal acne. The most common causes of infectious pustular skin lesions include bacterial infections, which may be initially localized (Staphylococcus aureus) or septicemic (with Listeria monocytogenes as the leading causitive agent); viral infections (herpes simplex, varicella-zoster, and cytomegalovirus infections); fungal infections (candidiasis); or parasitic disorders (scabies). The main objective of this article is to propose a systematic approach to pustular eruptions in the neonate. The need for investigating every neonate with pustules for an infectious disease is emphasized. The Tzanck smear, the Gram's stain, and a potassium hydroxide preparation are the most important quick diagnostic tests. The Tzanck smear is a very easy, rapid, and sensitive test for detection of a herpetic infection (multinucleated giant cells) as well as noninfectious pustular eruptions (eosinophils, neutrophils). Therefore the Tzanck smear should be the first test performed. Moreover, a Gram's stain and potassium hydroxide preparation should be performed in cases of neonatal pustular disorders to detect bacterial and fungal infections. The goal of this diagnostic approach is to spare a healthy neonate with a benign transient condition an invasive evaluation for sepsis, potentially harmful antibiotic therapy, and prolonged hospitalization, with its own inherent morbidity.