The sooner a cancer is detected, the easier it is to treat and developing tools for early cancer detection can ultimately help save lives. Capturing and sequencing of cell-free DNA (cfDNA) has emerged as a promising source of diagnostic information. Researchers are using custom target enrichment panels to extract and analyze DNA fragments shed from cancerous cells and captured in blood samples—enabling the use of liquid biopsies for less invasive and more sensitive screening. Additionally, advances in methylation sequencing workflows are improving cfDNA analysis by exposing epigenetic clues about the cancer’s subtype and tissue of origin. Together, custom target enrichment panels and methylation sequencing give researchers tools to develop more sensitive and specific early cancer detection assays.