The broad cellular tropism of human cytomegalovirus (HCMV) is a direct consequence of the multifaceted viral entry process involving a combination of viral glycoprotein and cellular receptor interactions that carefully orchestrate viral binding and penetration events. Although recent strides have been made in elucidating the molecular mechanisms of HCMV entry, it has become increasingly clear that the first step of the viral life cycle is exquisitely complex and dependent on several factors including virus strain and cell type. The lack of a full understanding about HCMV entry emphasizes the need for molecular techniques that can help to identify the specific roles of viral glycoproteins and cellular receptors during the viral entry process. Here, we describe various methodologies used in our laboratory and others to examine the different steps required for HCMV entry into target cells.