Cancer is one of the greatest threats posed to society, necessitating appropriate diagnosis methods. Modern targeted therapies have greatly advanced the treatment of several solid tumors. The rational use of these agents requires optimal strategies for the rapid and accurate detection of targetable genomic alterations at the time of initial diagnosis and when acquired resistance to targeted therapies develops. Currently used techniques, such as tissue genotyping, have limitations such as difficulty in categorizing tumors, needing frequent sampling, and difficulty in obtaining samples. To overcome these issues, cost-effective and non-invasive methods are an urgent requisite, which would provide an insight into the realtime dynamics of cancers via circulating biomarkers. Circulating tumor DNA (ctDNA), commonly termed "liquid biopsy," has emerged as a new, promising non-invasive tool to detect biomarkers in several cancers. The present review aimed to understand the biological concept of ctDNA and its potential as a biomarker in cancer studies and the clinical utility of this evolutionary diagnostic technique.