Recent developments in molecular genetics, including progress in the human genome project, have allowed identification of genes at an unprecedented rate. To date gene expression profiling studies have focused on identifying transcripts that are specifically or preferentially enriched within the inner ear on the assumption that they are more likely to be important for auditory and vestibular function. It is now apparent that some genes preferentially expressed in the cochleo-vestibular system are not crucial for hearing or balance or their functions are compensated for by other genes. In addition, transcripts expressed at low abundance in the inner ear are generally under-represented in gene profiling studies. In this review, we highlight the limitations of current gene expression profiling strategies as a discovery tool for genes involved in cochleo-vestibular development and function. We argue that expression profiling based on hierarchical clustering of transcripts by gene ontology, combined with tissue enrichment data, is more effective for inner ear gene discovery. This approach also provides a framework to assist and direct the functional characterization of gene products.