The spectral, spatial and temporal properties of the retinal mechanisms underlying circadian phase shifting and acute melatonin suppression by bright light are an important area of investigation. The photopigment melanopsin, expressed in a subset of retinal ganglion cells, rendering them intrinsically photosensitive, is thought to largely mediate these “non-image-forming” effects of light. Using the method of silent substitution, which allows for the targeted stimulation of melanopsin in humans, we have made progress in measuring and understanding the contributions of melanopsin to the pupillary light reflex and to primary visual cortex. A key focus has been on developing methods to assess the quality of isolation of melanopsin with minimal inadvertent stimulation of the cones. Future work using the silent substitution paradigm will tease apart the different photoreceptor contributions to the human circadian system.