This review summarizes the multiple roles of microRNAs (miRNAs) in the prediction and treatment of heart failure (HF), including the molecular mechanisms regulating cell apoptosis, myocardial fibrosis, cardiac hypertrophy, and ventricular remodeling, and highlights the importance of miRNAs in the prognosis of HF. In addition, the strategies for alleviating HF with miRNA intervention are discussed. On the basis of the challenges and emerging directions in the research and clinical practice of HF miRNAs, it is proposed that miRNA-based therapy could be a new approach for prevention and treatment of HF.