Liquid biopsies are best suited to monitor a patient’s tumor burden. Certain genetic alterations that are associated with therapy sensitivity and resistance can also be detected, and this information can provide therapeutic guidance for some patients. However, due to the low tumor DNA proportion in the blood, much information about genetic alterations in a patient’s tumor are lost in liquid biopsies compared to tumor samples. The gene number and exon coverage are limited in those assays, and the detection of copy number alterations remains difficult. For an evaluation of therapeutic choices, tumor samples should be used if available.