Photoreceptor degeneration in human photoreceptor dystrophies and in the relevant animal models has been thought to be executed by one common mechanism- caspase-mediated apoptosis. However, recent experiments have challenged this concept. Gene defects or environmental stressors appear to cause oxidative stress and altered metabolism, which appear to induce caspase-dependent and caspase-independent cell death mechanisms such as the activation of cysteine-proteases, lysosomal proteases and autophagy and possibly complement-mediated lysis. In this article, we point out mechanistic parallels between these pathways and summarize our recently published investigation using a temporal analysis of the different pathways, which suggests that the noncaspase-dependent mechanisms may actively participate in the demise of the photoreceptors rather than represent a passive response of the retina to the presence of dying cells. Our investigation revealed that unless the common upstream initiator for a given photoreceptor dystrophy can be found, multiple rescue paradigms need to be used to target all active pathways.