There is no arguing against Dr. Rich’s basic premise. The currently used end points are unquestionably flawed. The 6-min walk distance, which is the major outcome variable in most of the more recent clinical trials, is “affected by a multitude of factors, including age, gender, height, and weight.” Dr. Rich could also have mentioned that it is influenced by patient effort and musculoskeletal conditions, and has a ceiling effect.3 The World Health Organization functional class is no better; it is a blunt instrument that relies on subjective interpretation by both the patient and caregiver. Hemodynamic responses to therapy in the clinical trials have been, in Dr. Rich’s view, “unimpressive,” and the trials much too short. He bemoans the lack of any end points that reflect the true status of the disease such as assessments of vessel or cardiac structure, or molecular markers of the biological state of the disease. These are valid points.