Urothelial carcinoma of the bladder is the second most common genitourinary malignancy and the second most common cause of genitourinary cancer-related deaths with a worldwide estimate of about 300,000 new cases diagnosed every year. A significant problem in this type of cancer is the high recurrence rate of non-invasive primary tumors, leading to a high percentage of tumor progression and to a very poor 5-year survival rate. Targeted and gene therapy are currently the two major efforts in cancer treatment. Targeted therapy refers to strategies against specific cellular molecules deregulated in tumors, whereas gene therapy focuses on the genetic modification of tumor cells, mainly for correcting gene defects, inducing selective tumor cell death or modulating host's immune response. Recent advances in our understanding of the pathogenesis of bladder cancer at the molecular level have provided a significant number of cellular targets for therapy and have shown the importance of individualized therapy according to the molecular profile exhibited by the tumor cells. While the major problems of both targeted and gene therapy are far from being solved yet, both lines of cancer therapy hold promising results. This article aims at providing a brief general overview of this broad subject.