The prevalence of heart failure (HF) continues to grow in the USA, and approximately 50% of these patients are women. Despite this, there has been an underrepresentation of women in HF clinical trials, which has led to limitations in understanding of sex-related differences in HF pathophysiology, diagnosis, and treatment. The purpose of this review is to highlight the differences between men and women in various heart failure trials conducted in the last century and emphasize new findings from recent trials in the management of, and outcomes in, women with HF. HF trials have shown that women have improved survival with guideline-directed medical therapy, and the most recent analysis from PARADIGM-HF showed women had lower mortality and hospitalization rate compared with men. Furthermore, despite comprising only 20% of subjects in cardiac resynchronization therapy (CRT) trials, we now know that women are likely to benefit from a CRT device, in particular those with left bundle branch block. Advanced therapies for heart failure including durable mechanical circulatory support remain underused in women, and female patients are less likely to undergo heart transplantation when compared with men of similar risk profiles. The latest studies have shown women receiving continuous-flow left ventricular assist device support had lower chances of heart transplantation, increased risk of waitlist mortality, and higher rates of delisting for worsening clinical status. However, post transplantation, women have better survival when compared with men. Although several studies have shown that women with HF live longer than men, they experience greater self-reported psychological and physical disability and poorer overall quality of life. The cause of sex differences in morbidity and mortality remains unknown, but as the therapeutic options for HF expand, sex-based differences in treatment would need to be considered.