Clinical response to cardiac resynchronization therapy (CRT) has been known for years to be highly variable, with a spectrum of responses from no change or even deterioration of cardiac function to spectacular improvements. In the plethora of clinical, echocardiographic, biohumoral, and electrophysiological predictors of response to CRT and postimplant issues besides patient selection, the role of right ventricular (RV) function has been largely overlooked. In reviewing current evidence, we noticed conflicting results between observational studies and randomized trials not only concerning the impact of baseline RV function on CRT efficacy but also on the effects of CRT on RV size and function. Hence, we aimed to provide a critical reappraisal of current knowledge and unresolved issues on the reciprocal interactions between RV function and CRT, shifting the spotlight on the concept of right heart pulmonary circulation unit and on the clinical and prognostic significance of impaired ventricular-arterial coupling reserve. In this viewpoint, we propose that (1) CRT should not be denied to potential candidate because of “isolated” RV dysfunction and (2) assessment of baseline right heart pulmonary circulation unit and its dynamic response to pharmacological stress should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors.