Right-to-left pulmonary and cardiac shunts (RLS) are important causes of refractory hypoxia in the critically-ill perioperative patient. Using a point-of-care ultrasound (POCUS) agitated saline bubble study for an early diagnosis allows patients with clinically significant RLSs to receive expedited therapy. This narrative review discusses the principles of agitated saline ultrasonography as well as the role of POCUS in detecting the most common RLS types seen in the intensive care unit, including patent foramen ovale, atrial septal defects, and pulmonary arterio-venous malformations. An illustrated discussion of the procedure, as well as shunt-enhancing maneuvers (Valsalva or lung recruitment maneuver with subsequent rapid release) is provided. With the wide dissemination of bedside ultrasound within the perioperative and critical care arena, POCUS practitioners should be knowledgeable of the potential pitfalls leading to both false-positive and false-negative studies. False-positive studies may be due to congenital abnormalities, mischaracterization of intrapulmonary shunts as intracardiac shunts (and vice versa), or evidence of the Valsalva effect. False negatives are typically due to respiratory-phasic variation, performing an inadequate shunt-enhancing maneuver, inadequate injection of agitated saline, or pathophysiologic states of elevated left atrial pressure. Finally, alternative POCUS methods for determining presence of an RLS in patients with poor echocardiographic windows are discussed, with a focus on pulsed-wave Doppler interrogation of arterial signals.