Critically ill patients with the need for mechanical ventilation show complex interactions between respiratory and cardiovascular physiology. These interactions are important as they may guide the clinician’s therapeutic decisions and, possibly, affect patient outcome. The aim of the present review is to provide the practicing physician with an overview of the concepts of heart-lung interactions during mechanical ventilation. We outline the basic cardiac and respiratory physiology during spontaneous breathing and under mechanical ventilation. The main focus is on the interaction between positive pressure ventilation and its effects on right and left ventricular pre- and afterload and ventricular interdependence. Further we discuss different modalities to assess volume responsiveness, such as pulse pressure variation. We aim to familiarise the reader with cardiovascular side effects of mechanical ventilation when experiencing weaning problems or right heart failure.