Mutations in rhodopsin cause autosomal dominant retinitis pigmentosa. The majority of these mutations (class II) lead to protein misfolding. The misfolded protein is retained in the ER then retrotranslocated into the cytoplasm for degradation by the proteasome. If degradation fails, the protein can aggregate to form intracellular inclusions. In addition, the mutant rod opsin exerts a dominant negative effect on the wild-type protein. Here, we review these pathways and how different drug treatments can affect mutant rod opsin. Interestingly, drugs targeted at general protein stability (kosmotropes) or improving the cellular folding and degradation machinery (molecular chaperone inducers and autophagy induction) reduced P23H rod opsin aggregation and inclusion formation together with associated caspase activation and cell death, but did not enhance mutant protein processing or reduce the dominant negative effects. In contrast, pharmacological chaperones (retinoids) enhanced P23H folding and reduced the dominant negative effects, as well as reducing the other gains of function. Therefore, targeting the toxic gain of function did not require improved folding, whereas reducing the dominant negative effects required improved folding. These studies suggest that some forms of rhodopsin retinitis pigmentosa could be treated by targeting protein folding and/or reducing protein aggregation.