Transthoracic echocardiography (TTE) provides a comprehensive assessment of cardiac anatomy and cardiac hemodynamics that can diagnose the etiology of circulatory failure and guide therapeutic interventions. The increased accessibility of portable point-of-care ultrasound devices and the integration of clinical ultrasonography into critical care training programs have served to expand TTE fundamentals into the clinical workflow of intensive care medicine at large. Typically, in the intensive care unit, the hemodynamic parameter of principle interest is left ventricular systolic function. In general clinical practice, about 10–15% of patients have suboptimal transthoracic imaging windows that limit endocardial resolution and preclude accurate assessment of left ventricular systolic function (Kurt et al., J Am Coll Cardiol 53(9):802–10, 2009). Technically limited or nondiagnostic TTE exams are even more prevalent in the intensive care unit (30–40%) due to multiple clinical factors including lung disease, mechanical ventilation, and postoperative incision dressings (Hwang et al., Korean Circ J 45(6):486, 2015; Kurt et al., J Am Coll Cardiol 53(9):802–10, 2009; Reilly et al., J Am Coll Cardiol 35(2):485–90, 2000). Given the high percentage of potentially suboptimal TTE studies in the intensive care unit, it is important that critical care providers are familiar with methods to improve endocardial definition and well versed in alternative approaches for evaluation of left ventricular systolic function. In addition to discussing the importance of patient positioning for image optimization, this chapter will emphasize the use of ultrasound enhancement agents for salvaging technically limited or challenging echocardiograms. Evaluation of left ventricular systolic function using highly feasible non-B-mode (2D) echocardiographic methods such as M-mode (mitral annular plane systolic excursion, E-point septal separation) and Doppler (dP/dt, stroke volume, myocardial performance index) will be reviewed. These alternative echocardiographic parameters can help guide clinical decision-making by discriminating normal left ventricular systolic function from severely reduced systolic function.