The urinary bladder is a hollow organ which comprises mainly of smooth muscle cells (SMC). The relaxation and contraction of urinary bladder smooth muscle allows the bladder to store and void urine, respectively. Phenotypic modulation of bladder SMC and the expression of inducible nitric oxide synthase are related with various pathological conditions, including bladder dysfunction. Hypoxia inhibits human bladder SMC proliferation upregulating also survival factors such as HIF1 alpha and VEGF. The secretory phenotype of the bladder SMC extracellular matrix depends on the frequency of mechanical deformation experienced by these cells. SMC proliferation is a major contributing factor to the development and progression of a variety of diseases. As a result, understanding SMC changes during the genesis and maintenance of disease is vital to the development of therapeutic approaches. Immortalized Human Bladder Smooth Muscle Cells are also useful tools to develop disease models for High Throughput and High Content Screening.