Immune-modulation therapy has had great success in various inflammatory diseases. Despite the promising results of preliminary studies in anti-tumor necrosis factor-α therapies, large randomized studies have lacked positive clinical outcomes in patients with heart failure. These results have led to the idea that therapies directed toward specific inflammatory mediators may not be the answer and lead us toward the development of novel anti-inflammatory strategies that may involve a broader spectrum of inflammatory mediators. Therapeutic plasma exchange has been demonstrated as a safe treatment, and preliminary outcomes led us to develop new treatment schemes.