The retina provides exquisitely sensitive vision that relies on the integrity of a uniquely vulnerable cell, the photoreceptor (PR). The genetic and mechanistic causes of retinal degeneration due to PR cell death--which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration--are being successfully dissected. Over one hundred loci, some containing common variants but most containing rare variants, are implicated in the genetic architecture of this complex trait. This genetic heterogeneity results in equally diverse disease mechanisms that affect almost every aspect of PR function but converge on a common cell death pathway. Although genetic and mechanistic diversity creates challenges for therapy, some approaches--particularly gene-replacement therapy--are showing considerable promise.