Complex cystic and cystic-like focal liver lesions (FLLs) encompass a spectrum of disorders ranging from non-neoplastic conditions to benign and malignant tumors. In this prospective, the possibility of non-invasive differentiation of these lesions is extremely important, because the clinical implications and therapeutic strategies vary considerably. Because of its advantageous cost/benefit ratio, widespread availability and easy execution, ultrasound (US) is the first-line imaging modality in most countries for the initial liver survey and represents the imaging technique that usually detects a complex liver cyst. However, US showed poor efficacy in the differential diagnosis of complex cystic FLLs. Thus, for years, computed tomography (CT) and magnetic resonance (MR) imaging have been used for further assessment of these lesions. Recently, the development of low mechanical index real-time contrast-enhanced ultrasound (CEUS) technique performed with the second generation of US contrast agents has led to an accurate depiction of macrovasculature and microvasculature. The technique yields information about contrast enhancement of the liver and FLLs almost as CT and MRI do, but in real time and without the use of ionizing radiation. To date, there is only a small amount of evidence about the role of CEUS in the less common setting of complex liver cysts. The aim of this review is to offer an up-to-date overview on the state of the art of CEUS in the study of the most common complex cystic focal liver lesions. To our knowledge, there are no literature comprehensive reviews on this topic.