Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is 
a highly effective treatment for carcinoma in situ of the bladder, as well as 
high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 
30 years of clinical experience with BCG, the therapy's mechanism has remained 
enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy 
have led to exciting discoveries regarding the potential role of tumor necrosis 
factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic 
benefit of BCG immunotherapy. In this paper, we will review the scope of the 
disease, highlight our understanding of the role for BCG in urothelial carcinoma 
of the bladder, explain the recent discoveries regarding the role of neutrophils 
and TRAIL in therapy, and theorize on potential future areas of research.