Purpose of review The discovery of a new class of intrinsically photosensitive retinal ganglion cells (ipRGCs) revealed their superior role for various nonvisual biological functions, including the pupil light reflex, and circadian photoentrainment. Recent findings Recent works have identified and characterized several anatomically and functionally distinct ipRGC subtypes and have added strong new evidence for the accessory role of ipRGCs in the visual system in humans. Summary This review summarizes current concepts related to ipRGC morphology, central connections and behavioural functions and highlights recent studies having clinical relevance to ipRGCs. Clinical implications of the melanopsin system are widespread, particularly as related to chronobiology.