CRISPR/Cas-mediated genome editing is an effective and attractive tool for the treatment of diseases or genes that cannot be adequately covered by gene replacement strategies. The first FDA-approved AAV-vector- and CRISPR/Cas-based clinical trials were each designed for the treatment of a subtype of an inherited retinal dystrophy, underscoring the importance of ophthalmic diseases in the field of gene (editing) therapies. This and most other pre-clinical therapeutic CRISPR/Cas approaches are typically designed for the treatment of single mutations. For the treatment of larger patient cohorts, however, mutation- or ideally gene-independent approaches appear to be more suitable. CRISPR/Cas-mediated transcriptional activation of genes (CRISPRa) is a promising approach to achieve these ambitious goals. In this minireview, focusing on inherited retinal dystrophies, we will discuss recent developments, advantages and limitations, and future prospects of CRISPRa as a therapeutic tool.