AFLP-PCR is a PCR-based tool used in genetics research, DNA fingerprinting, and in the practice of genetic engineering. AFLP uses restriction enzymes to digest genomic DNA, followed by ligation of adaptors to the sticky ends of the restriction fragments. The key feature of AFLP-PCR is its capacity for the simultaneous screening of many different DNA regions distributed randomly throughout the genome. To achieve high reliability of the screen, genomic DNA is prepared in an ingenious, but technically straight forward, way that combines the strengths of two methods, the replicability of restriction fragment analysis and the power of the PCR. This chapter describes AFLP and its use in the cystic fibrosis disease.