Liquid biopsy provides the opportunity of detecting, analyzing and monitoring cancer in various body effluents such as blood or urine instead of a fragment of cancer tissue. It is composed of different biological matrices such as circulating tumor cells (CTCs), cell free nucleic acids, exosomes or tumors “educated platelets.” In addition to representing a non- or minimally invasive procedure, it should represent a better view of tumor heterogeneity and allows for real-time monitoring of cancer evolution. Recent technological and molecular advances, greatly facilitated by the use of microfluidics in many cases, have permitted large progresses both in our ability to purify and analyze liquid biopsy components. In particular, the great developments of droplet-based digital PCR and the various optimizations of next generation sequencing technologies are central to the several validations of CTC-free DNA as a strong cancer biomarker. However, complete adoption of liquid biopsy in clinics will require pursuing recent efforts in the standardization of procedures both on the pre-analytical and analytical aspects.