Heart failure (HF), the final stage of pathological cardiac hypertrophy, is a major cause of hospitalization and mortality. The role of inflammation in the pathogenesis of HF has been extensively studied, with great emphasis on proinflammatory cytokines. Yet, clinical trials targeting these cytokines failed to become a credible therapeutic strategy for HF. More recent studies are increasingly highlighting an active role for T cells in the progression of HF pathology. As a result, a number of novel immunotherapy strategies are emerging for the treatment of HF and other cardiovascular diseases, via the targeting of adaptive immunity. Here we provide an overview of the background, details, and expected outcomes of these attempts.