Congestive heart failure is a common clinical problem resulting in significant morbidity and mortality. Although considerable progress has been made in elucidating the pathophysiologic mechanisms that lead to the development of this process, much remains unknown. The techniques of modern molecular biology now allow a detailed and systematic analysis of this disease. Recent data linking cardiac hypertrophy, aberrant signaling, or cytoskeletal abnormalities to the development of heart failure have provided new insights into this process. These studies have confirmed the importance of many classical pathways but also revealed novel pathways. This review will focus on the recent advances that have been made and will highlight the importance they have had in our understanding and treatment of heart failure.