The treatment of bladder dysfunction continues to evolve. Despite progress in the development of oral pharmacologic therapies, available treatments for this common urologic condition have contraindications, untoward side effects, or limited efficacy in certain patient populations. Recent advances in the understanding of the mechanistic basis for bladder disorders have prompted researchers to seek more targeted molecular therapies. The goal of these next-generation therapies is to selectively modulate/alter gene expression in somatic cells to normalize aberrant cellular responses. This treatment modality, termed “gene therapy” or “gene transfer,” is the subject of this review. The bladder is an ideal target for gene transfer as the genetic material can be locally administered, removing a major therapeutic obstacle, namely systemic delivery. The recent completion of the first phase I clinical trial for a gene transfer treatment of another common urologic disease, namely, erectile dysfunction, speaks to the maturation of this technology and its translation from the laboratory to the clinic. As discussed in this report, the continuing evolution of gene transfer vectors and gene delivery technologies is expected to further enhance the selectivity, efficacy, and duration of gene therapy, making it a viable treatment option for the amelioration of lower urinary tract diseases/disorders.