To discuss the value and limitations of interpreting small case series for the purpose of understanding the pathophysiology of conditions affecting the visual system and how they may influence patient care decision making DESIGN: Selective review of English language ophthalmic articles published in peer review journals since 1950.Author initiated PubMed Central query of small case series in glaucoma, pediatric neuro-ophthalmology, and diabetic retinopathy RESULTS: A review of well-known ophthalmic case studies by Gass, Irvine, Brockhurst and others show that small samples can provide suggestions to the skilled clinician for adding steps to the examination process when uncovering rare or previously unknown associated complications, as is the case for this perspective's initiating studies by Groth and Brodsky. However, as shown by the now-retracted small case series in Lancet connecting MMR vaccinations with autism, small case series do not replace the value of clinical trials, with rare exception, when considering impacts to widespread, common clinical practice.Small case series may contribute to an improved understanding of pathophysiology of rare ophthalmic conditions, but alone are insufficient to provide evidence for changing clinical practice of common eye diseases.