Bladder cancer is the 9th most common tumour worldwide with Urothelial Carcinoma (UC) being the most frequent type of the disease. Cisplatin-based chemotherapy is the standard of care in advanced and metastatic UC. However, its therapeutic efficacy is limited by chemoresistance. Cisplatin-resistant UC cell lines were generated to investigate underlying mechanisms and to develop new approaches for overcoming resistance. Interestingly, each cisplatin-resistant cell line contained an individual assortment of resistance mechanisms at multiple levels. This heterogeneity among several cell lines of the same tumour entity may be responsible for the complicated scenario, which can be observed in the clinic.