Histologic characterization of urothelial carcinoma remains the most important factor for determining a patient's prognosis and treatment regimen. However, challenges remain in accurately staging and grading many tumors, and substaging remains controversial. Recently, significant insight has been gained into the molecular pathogenesis of bladder cancer that may aid in further characterizing urothelial carcinoma. Many molecular biomarkers have been clinically validated, and some have been shown to provide more prognostic information than histology alone. In addition, a subset of these markers may even represent targets for molecular therapy. Here, we review histologic staging and grading of urothelial carcinoma, as well as discuss many of the clinically relevant molecular markers. As each urothelial carcinoma likely represents a unique biological entity, the need for complete histologic and molecular characterization of these tumors is necessary as we enter the age of personalized medicine.