Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.