The pathological mechanisms involved in Heart failure (HF) are complex and remain controversial. Caused by a variety of predisposing and exacerbating factors for HF development, the selection of animal models in current preclinical R&D has been a major challenge. In this review, we give a comprehensive overview of different models in various species currently used in HF research, and discuss their general applicability. In addition, we summarize the preclinical research review of approved drugs for HF, which provides theoretical and practical guidance for researchers considering preclinical studies for the treatment of HF.