Cancer is one of the greatest threat facing our society, being the second leading cause of death globally. Currents strategies for cancer diagnosis consist of the collection of a solid tissue from the affected area. But solid biopsy is associated with various risky complications such aspainful tissue collection, time-consuming and expensive processes, in some cases, the extracted tissue is not sufficient for the molecular study of cancer. New alternatives that overcome these drawbacks of solid biopsy are rising up nowadays, such as liquid biopsy. Liquid biopsy provides an opportunity to detect, analyze, and monitor cancer in various body effluents such as blood, saliva, stool, and urine, which are composed of different biological matrices such as circulating tumor cells (CTCs), circulating tumor-specific nucleic acids (circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), microRNAs (miRNAs), long non-coding RNAs (lnRNAs)), exosomes, and autoantibodies. These circulating biomarkers play a key role in understanding tumorigenesis andmetastasis, which provides a better insight into the evolution of the tumor dynamics during disease progression and treatment. Herein, we provide a comprehensive overview of the biogenesis, their current detection methods, and importance of each biomolecule in liquid biopsy technique.