One of the most important attributes of the polymerase chain reaction (PCR) is its exquisite sensitivity. However, the high sensitivity of PCR also renders it prone to false-positive results because of, for example, exogenous contamination. Good laboratory practice and specific anti-contamination strategies are essential to minimize the chance of contamination. Some of these strategies, for example, physical separation of the areas for the handling samples and PCR products, may need to be taken into consideration during the establishment of a laboratory. In this chapter, different strategies for the detection, avoidance, and elimination of PCR contamination will be discussed.