There is an incessant need to improve upon and optimize patient care in oncology. Better understanding patient prognosis and survival can help treatment become more personalized and effective. As such, tracking patient response to specific chemotherapy drugs during cancer treatment is crucial for outpacing tumor evolution and maximizing patient survival. Traditionally, treatment efficacy is determined by measuring changes in tumor size over the course of treatment with imaging. However, imaging techniques are, in part, qualitative, and are also imperfect at distinguishing true tumor progression from pseudoprogression, i.e. apparent progression of the tumor that dissipates in time and does not indicate cancer progression. Pseudoprogression that is misinterpreted as true progression may force patients to undergo unnecessary surgeries and procedures that hinder their long-term recovery and survival. This necessitates quick and accurate quantitative markers for tumor burden. Among the most promising of these biomarkers is cell-free DNA, unbound small-fragment DNA present in circulation that is released into the blood as a result of apoptosis, necrosis, as well as other factors not yet well understood. Cell-free DNA can be extracted from several body regions; origin may depend on cancer type. Multiple studies across a variety of cancers have demonstrated associations between the concentration of cell-free DNA and prognosis and progression of the disease. These studies have shown that high levels of cell-free DNA have a statistically significant association with poor overall survival (OS) and progression-free survival (PFS) when compared to low cell-free DNA levels. Concentrations of plasma cfDNA can also indicate changes in tumor size during treatment, in some instances even preceding tumor growth as assessed by imaging. Further inquiry into the use of cfDNA concentration as a surrogate for tumor size and an indicator of prognosis is certainly worthwhile, and this subsequent review will highlight major findings in the field that support this notion.