ABSTRACT Introduction Approximately 30–60% of patients treated with Bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer (NMIBC) eventually experience disease recurrence within 2 years. Parsimonious use of BCG and accurate identification of those patients who might benefit from this therapy is of paramount importance in order to avoid BCG wastage, improve patient counseling regarding alternative therapy, patient’s survival and quality of life. We summarized the current literature on predictive and prognostic models on intravesical BCG therapy for NMIBC. Areas covered Clinicopathologic features are the strongest predictors of BCG response. In addition, several tissue, serum and urinary biomarkers have been investigated. However, they have not been shown to be robust enough to be implemented in daily clinical routine. Therefore, genetic and epigenetic markers and features of the tumor microenvironment have been investigated. The relationship between Th1 and Th2 microenvironments, as well as its related serum and urine biomarkers, was shown to play an important role in prediction of response to BCG treatment. Expert opinion No single tumor biomarker has been shown to be robust enough to change clinical decision making. Discoveries in the genetic signature profile of bladder cancer and immunological pathways represent the new frontiers in biomarker discovery and possible improvement in patient selection in the era of personalized medicine.