Cardiac resynchronization therapy (CRT) is a well established option in patients with moderate to severe heart failure on optimal medical therapy, NYHA functional class Ill-IV, reduced systolic function (left ventricular ejection fraction < or =35%), broad QRS complex (>120 ms), but data addressing sex differences in response to CRT are lacking. Women are underrepresented in clinical and observational trials on CRT (<30%) but, when examining response across recent studies, there is evidence of a more positive effect of CRT in women. Also our data show that females seem to achieve a greater survival benefit with CRT than male recipients. While larger trials remain the ideal way to specifically address the question of a gender effect, with some uncertainties on the understanding of the greater benefit still present (specific factors intrinsic to women are responsible for this difference? pre-CRT clinical characteristics, prevalence of nonischemic cardiomyopathy and left bundle branch block, other than female gender itself?), current evidence supports the notion of increasing access to CRT for women with the appropriate indication, to allow them to exploit the distinctive benefits associated with this treatment strategy.